Trial Outcomes & Findings for To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes (NCT NCT01725126)

Results Overview

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Up to Follow-up (8 weeks)

Results posted on

2017-12-13

Participant Flow

The study was conducted in 3 parts in healthy male and female participants aged 18 to 70 years in Part A and in participants with type 2 diabetes (T2D) in Part B and C across three centers of United States of America.

A total of 15 participants were randomized in Part A, 20 were randomized in Part B and 18 were randomized in Part C.

Participant milestones

Participant milestones
Measure	Part A-Placebo Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 gram (g) kit twice daily (BID) for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 milliliter (mL) of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) prior to breakfast (morning) and 10 g (2 unit) prior to dinner (evening). On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 milligram (mg) immediate release (IR) tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part A-GSK2890457 Healthy participants received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, GSK2890457 was given in the evening.	Part B-Placebo+Liraglutide Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 milligram (mg) once daily by subcutaneous injection during the Treatment period along with placebo.	Part B-GSK2890457+Liraglutide Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Overall Study STARTED	4	11	6	14	6	12
Overall Study COMPLETED	4	10	6	13	6	12
Overall Study NOT COMPLETED	0	1	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A-Placebo Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 gram (g) kit twice daily (BID) for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 milliliter (mL) of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) prior to breakfast (morning) and 10 g (2 unit) prior to dinner (evening). On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 milligram (mg) immediate release (IR) tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part A-GSK2890457 Healthy participants received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, GSK2890457 was given in the evening.	Part B-Placebo+Liraglutide Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 milligram (mg) once daily by subcutaneous injection during the Treatment period along with placebo.	Part B-GSK2890457+Liraglutide Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Overall Study Protocol Violation	0	1	0	0	0	0
Overall Study Withdrawal by Subject	0	0	0	1	0	0

Baseline Characteristics

To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part A-GSK2890457 n=11 Participants Healthy participants received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, GSK2890457 was given in the evening.	Part B-Placebo+Liraglutide n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 milligram (mg) once daily by subcutaneous injection during the Treatment period along with placebo.	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.	Total n=53 Participants Total of all reporting groups
Age, Customized 18 to 70 years	4 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants	6 Participants n=21 Participants	12 Participants n=8 Participants	53 Participants n=8 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=8 Participants	15 Participants n=8 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	10 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants	3 Participants n=21 Participants	8 Participants n=8 Participants	38 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	11 Participants n=8 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants	6 Participants n=21 Participants	10 Participants n=8 Participants	42 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (8 weeks)

Population: All Subjects Population comprised of all randomized participants who received at least one dose of study medication (placebo or GSK2890457).

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A Any AE	10 Participants	—	3 Participants	—
Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A Any SAE	0 Participants	—	0 Participants	—
Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A Any Death	0 Participants	—	0 Participants	—

PRIMARY outcome

Timeframe: Up to Follow-up (8 weeks)

Population: All Subjects Population.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as ALT \>=3 x ULN, and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Any AE, SAE or Death During Part B and Part C Any AE	3 Participants	3 Participants	1 Participants	3 Participants
Number of Participants With Any AE, SAE or Death During Part B and Part C Any SAE	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Any AE, SAE or Death During Part B and Part C Any Death	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (8 weeks)

Population: All Subjects Population.

Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of complete blood count (CBG) or plasma glucose value of \<50 milligram per deciliter (mg/dL) for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting).

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Any Hypoglycemic Events During Part A	0 Participants	—	0 Participants	—

PRIMARY outcome

Timeframe: Up to Follow-up (8 weeks)

Population: All Subjects Population.

Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of CBG or plasma glucose value of \<50 mg/dL for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting).

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Any Hypoglycemic Events During Part B and Part C	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALT, Day 42	1.0 IU/L Standard Deviation 10.21	-0.5 IU/L Standard Deviation 6.35	-4.3 IU/L Standard Deviation 5.13	-4.2 IU/L Standard Deviation 7.79
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C AST, Day 28	2.2 IU/L Standard Deviation 4.74	0.7 IU/L Standard Deviation 7.61	-2.0 IU/L Standard Deviation 4.86	1.4 IU/L Standard Deviation 4.85
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C AST, Day 42	3.8 IU/L Standard Deviation 8.19	1.0 IU/L Standard Deviation 4.38	-3.8 IU/L Standard Deviation 5.08	1.9 IU/L Standard Deviation 4.94
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C AST, Day 7	1.1 IU/L Standard Deviation 2.66	-0.5 IU/L Standard Deviation 7.20	-1.2 IU/L Standard Deviation 7.39	0.2 IU/L Standard Deviation 3.04
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C AST, Day 14	1.9 IU/L Standard Deviation 3.63	-1.0 IU/L Standard Deviation 14.76	-1.3 IU/L Standard Deviation 5.96	-0.3 IU/L Standard Deviation 6.02
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALP, Day 7	5.5 IU/L Standard Deviation 7.68	1.8 IU/L Standard Deviation 9.62	5.3 IU/L Standard Deviation 11.86	-2.2 IU/L Standard Deviation 9.35
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALP, Day 14	1.8 IU/L Standard Deviation 5.42	6.7 IU/L Standard Deviation 4.03	5.2 IU/L Standard Deviation 9.45	-3.7 IU/L Standard Deviation 17.92
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALP, Day 28	2.8 IU/L Standard Deviation 8.88	6.3 IU/L Standard Deviation 15.83	-0.3 IU/L Standard Deviation 6.89	-2.5 IU/L Standard Deviation 7.78
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALP, Day 42	2.2 IU/L Standard Deviation 5.58	0.5 IU/L Standard Deviation 8.50	4.3 IU/L Standard Deviation 8.69	-2.8 IU/L Standard Deviation 9.53
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALT, Day 7	-0.1 IU/L Standard Deviation 3.05	1.5 IU/L Standard Deviation 4.85	-1.3 IU/L Standard Deviation 4.84	-1.0 IU/L Standard Deviation 4.61
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALT, Day 14	0.6 IU/L Standard Deviation 5.75	3.0 IU/L Standard Deviation 10.99	-2.3 IU/L Standard Deviation 5.54	-6.3 IU/L Standard Deviation 13.85
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C ALT, Day 28	0.9 IU/L Standard Deviation 6.70	0.7 IU/L Standard Deviation 2.80	-2.5 IU/L Standard Deviation 4.18	-3.8 IU/L Standard Deviation 9.63
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C GGT, Day 7	-1.2 IU/L Standard Deviation 3.26	0.3 IU/L Standard Deviation 1.97	0.7 IU/L Standard Deviation 0.82	1.3 IU/L Standard Deviation 3.11
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C GGT, Day 14	-1.4 IU/L Standard Deviation 5.11	5.3 IU/L Standard Deviation 9.33	0.8 IU/L Standard Deviation 1.33	2.3 IU/L Standard Deviation 12.74
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C GGT, Day 28	0.8 IU/L Standard Deviation 2.80	2.3 IU/L Standard Deviation 5.68	0.0 IU/L Standard Deviation 2.45	0.5 IU/L Standard Deviation 4.01
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C GGT, Day 42	0.2 IU/L Standard Deviation 4.18	-0.7 IU/L Standard Deviation 4.55	-0.7 IU/L Standard Deviation 2.34	-0.9 IU/L Standard Deviation 4.52

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at on Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Carbon dioxide/Bicarbonate, Day 14	-1.9 mmol/L Standard Deviation 3.32	-2.0 mmol/L Standard Deviation 3.10	-1.8 mmol/L Standard Deviation 1.94	-0.7 mmol/L Standard Deviation 2.42
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Calcium, Day 7	0.053 mmol/L Standard Deviation 0.0763	0.025 mmol/L Standard Deviation 0.0879	0.083 mmol/L Standard Deviation 0.0604	-0.004 mmol/L Standard Deviation 0.0991
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Calcium, Day 14	0.041 mmol/L Standard Deviation 0.1079	0.067 mmol/L Standard Deviation 0.0700	0.050 mmol/L Standard Deviation 0.0985	0.017 mmol/L Standard Deviation 0.1215
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Calcium, Day 28	0.046 mmol/L Standard Deviation 0.1063	0.004 mmol/L Standard Deviation 0.0695	0.021 mmol/L Standard Deviation 0.0677	0.035 mmol/L Standard Deviation 0.1352
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Calcium, Day 42	-0.040 mmol/L Standard Deviation 0.1168	-0.071 mmol/L Standard Deviation 0.0533	-0.025 mmol/L Standard Deviation 0.0523	-0.056 mmol/L Standard Deviation 0.0775
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Chloride, Day 7	-1.2 mmol/L Standard Deviation 1.48	0.8 mmol/L Standard Deviation 2.93	-1.5 mmol/L Standard Deviation 1.38	0.4 mmol/L Standard Deviation 1.51
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Chloride, Day 14	-0.1 mmol/L Standard Deviation 1.96	0.5 mmol/L Standard Deviation 2.07	-0.8 mmol/L Standard Deviation 2.64	0.6 mmol/L Standard Deviation 1.88
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Chloride, Day 28	0.2 mmol/L Standard Deviation 1.17	1.0 mmol/L Standard Deviation 2.45	0.8 mmol/L Standard Deviation 2.79	0.3 mmol/L Standard Deviation 1.50
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Chloride, Day 42	0.2 mmol/L Standard Deviation 1.96	0.5 mmol/L Standard Deviation 2.35	-1.0 mmol/L Standard Deviation 2.10	0.3 mmol/L Standard Deviation 0.98
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Carbon dioxide/Bicarbonate, Day 7	-2.0 mmol/L Standard Deviation 3.53	-2.0 mmol/L Standard Deviation 2.00	0.0 mmol/L Standard Deviation 2.10	-0.6 mmol/L Standard Deviation 2.11
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Carbon dioxide/Bicarbonate, Day 28	-0.4 mmol/L Standard Deviation 2.47	-2.3 mmol/L Standard Deviation 2.34	-1.0 mmol/L Standard Deviation 2.28	-0.3 mmol/L Standard Deviation 2.83
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Carbon dioxide/Bicarbonate, Day 42	-1.8 mmol/L Standard Deviation 1.91	-2.8 mmol/L Standard Deviation 2.14	0.5 mmol/L Standard Deviation 2.59	-1.3 mmol/L Standard Deviation 3.14
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Glucose, Day 7	0.3 mmol/L Standard Deviation 3.29	0.9 mmol/L Standard Deviation 2.41	-0.3 mmol/L Standard Deviation 1.32	-1.7 mmol/L Standard Deviation 1.86
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Glucose, Day 14	0.2 mmol/L Standard Deviation 2.10	0.5 mmol/L Standard Deviation 2.06	-0.1 mmol/L Standard Deviation 1.17	-2.2 mmol/L Standard Deviation 2.44
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Glucose, Day 28	-0.2 mmol/L Standard Deviation 2.31	1.5 mmol/L Standard Deviation 2.71	-0.1 mmol/L Standard Deviation 1.71	-2.0 mmol/L Standard Deviation 2.76
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Magnesium, Day 7	0.0294 mmol/L Standard Deviation 0.04394	0.0206 mmol/L Standard Deviation 0.05034	0.0206 mmol/L Standard Deviation 0.05665	-0.0206 mmol/L Standard Deviation 0.08496
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Glucose, Day 42	-0.1 mmol/L Standard Deviation 2.30	1.2 mmol/L Standard Deviation 0.70	0.2 mmol/L Standard Deviation 1.06	0.1 mmol/L Standard Deviation 1.62
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Potassium, Day 7	0.09 mmol/L Standard Deviation 0.369	0.28 mmol/L Standard Deviation 0.264	0.33 mmol/L Standard Deviation 0.301	0.06 mmol/L Standard Deviation 0.368
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Potassium, Day 14	0.20 mmol/L Standard Deviation 0.353	0.17 mmol/L Standard Deviation 0.427	0.17 mmol/L Standard Deviation 0.258	0.07 mmol/L Standard Deviation 0.355
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Potassium, Day 28	0.08 mmol/L Standard Deviation 0.365	0.10 mmol/L Standard Deviation 0.253	0.28 mmol/L Standard Deviation 0.172	-0.07 mmol/L Standard Deviation 0.352
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Potassium, Day 42	0.01 mmol/L Standard Deviation 0.266	-0.05 mmol/L Standard Deviation 0.302	-0.05 mmol/L Standard Deviation 0.266	0.08 mmol/L Standard Deviation 0.564
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Magnesium, Day 14	0.0176 mmol/L Standard Deviation 0.06184	0.0069 mmol/L Standard Deviation 0.05463	-0.0206 mmol/L Standard Deviation 0.07236	0.0206 mmol/L Standard Deviation 0.11153
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Magnesium, Day 28	0.0379 mmol/L Standard Deviation 0.08951	0.0411 mmol/L Standard Deviation 0.09005	0.0274 mmol/L Standard Deviation 0.08879	0.0240 mmol/L Standard Deviation 0.11284
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Magnesium, Day 42	0.0063 mmol/L Standard Deviation 0.06014	-0.0274 mmol/L Standard Deviation 0.03356	-0.0137 mmol/L Standard Deviation 0.07197	-0.0171 mmol/L Standard Deviation 0.09349
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Sodium, Day 7	0.2 mmol/L Standard Deviation 2.58	1.3 mmol/L Standard Deviation 1.51	1.2 mmol/L Standard Deviation 2.04	0.8 mmol/L Standard Deviation 1.70
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Sodium, Day 14	1.4 mmol/L Standard Deviation 2.98	1.5 mmol/L Standard Deviation 1.05	1.3 mmol/L Standard Deviation 1.97	1.5 mmol/L Standard Deviation 2.07
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Sodium, Day 28	1.7 mmol/L Standard Deviation 2.87	1.0 mmol/L Standard Deviation 1.26	1.8 mmol/L Standard Deviation 1.94	0.6 mmol/L Standard Deviation 1.16
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Sodium, Day 42	-0.4 mmol/L Standard Deviation 2.90	-1.0 mmol/L Standard Deviation 1.79	0.5 mmol/L Standard Deviation 0.84	-1.0 mmol/L Standard Deviation 2.09
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Urea/BUN, Day 7	0.383 mmol/L Standard Deviation 1.0522	0.179 mmol/L Standard Deviation 0.6679	-0.000 mmol/L Standard Deviation 0.7140	-0.208 mmol/L Standard Deviation 1.0597
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Urea/BUN, Day 14	0.128 mmol/L Standard Deviation 0.9456	0.178 mmol/L Standard Deviation 1.9258	-0.297 mmol/L Standard Deviation 0.9423	-0.268 mmol/L Standard Deviation 1.1804
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Urea/BUN, Day 28	0.302 mmol/L Standard Deviation 0.7552	0.714 mmol/L Standard Deviation 2.0195	0.119 mmol/L Standard Deviation 1.8435	0.863 mmol/L Standard Deviation 1.3223
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Urea/BUN, Day 42	-0.412 mmol/L Standard Deviation 0.8603	-0.655 mmol/L Standard Deviation 0.4745	-0.595 mmol/L Standard Deviation 0.4323	-0.387 mmol/L Standard Deviation 1.0035
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Cholesterol, Day 42	-0.103 mmol/L Standard Deviation 0.4579	-0.052 mmol/L Standard Deviation 0.2560	-0.853 mmol/L Standard Deviation NA Only one participant was analyzed at this time point.	-0.155 mmol/L Standard Deviation 0.4389
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Phosphorus inorganic, Day 7	0.01 mmol/L Standard Deviation 0.089	-0.03 mmol/L Standard Deviation 0.186	0.10 mmol/L Standard Deviation 0.144	0.01 mmol/L Standard Deviation 0.116
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Phosphorus inorganic, Day 14	0.05 mmol/L Standard Deviation 0.090	-0.10 mmol/L Standard Deviation 0.193	0.01 mmol/L Standard Deviation 0.069	0.03 mmol/L Standard Deviation 0.143
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Phosphorus inorganic, Day 28	-0.01 mmol/L Standard Deviation 0.162	-0.12 mmol/L Standard Deviation 0.187	0.06 mmol/L Standard Deviation 0.107	0.12 mmol/L Standard Deviation 0.116
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C Phosphorus inorganic, Day 42	-0.04 mmol/L Standard Deviation 0.153	-0.05 mmol/L Standard Deviation 0.097	0.01 mmol/L Standard Deviation 0.053	-0.00 mmol/L Standard Deviation 0.094

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Uric acid, Day 28	16.9 umol/L Standard Deviation 45.09	-13.9 umol/L Standard Deviation 54.60	2.0 umol/L Standard Deviation 61.78	34.7 umol/L Standard Deviation 41.27
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Uric acid, Day 42	7.8 umol/L Standard Deviation 38.35	9.9 umol/L Standard Deviation 11.70	-5.0 umol/L Standard Deviation 29.96	0.5 umol/L Standard Deviation 26.78
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Uric acid, Day 7	25.1 umol/L Standard Deviation 30.26	3.0 umol/L Standard Deviation 52.09	15.9 umol/L Standard Deviation 54.73	9.9 umol/L Standard Deviation 34.81
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Uric acid, Day 14	15.3 umol/L Standard Deviation 35.74	-21.8 umol/L Standard Deviation 55.88	-11.9 umol/L Standard Deviation 37.43	25.3 umol/L Standard Deviation 50.03
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Direct bilirubin, Day 7	-0.208 umol/L Standard Deviation 0.6646	-0.513 umol/L Standard Deviation 1.3594	0.542 umol/L Standard Deviation 1.4118	-0.200 umol/L Standard Deviation 0.9530
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Direct bilirubin, Day 14	-0.305 umol/L Standard Deviation 0.6578	-0.086 umol/L Standard Deviation 0.1431	0.314 umol/L Standard Deviation 0.6876	-0.185 umol/L Standard Deviation 0.9379
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Direct bilirubin, Day 28	-0.197 umol/L Standard Deviation 1.1823	-0.171 umol/L Standard Deviation 1.1598	0.513 umol/L Standard Deviation 0.9366	-0.014 umol/L Standard Deviation 0.7732
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Direct bilirubin, Day 42	-0.197 umol/L Standard Deviation 0.5708	-0.200 umol/L Standard Deviation 0.7978	0.599 umol/L Standard Deviation 0.8635	-0.328 umol/L Standard Deviation 0.6780
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Total bilirubin, Day 7	-0.855 umol/L Standard Deviation 2.2991	-3.705 umol/L Standard Deviation 4.8867	0.570 umol/L Standard Deviation 5.9891	0.000 umol/L Standard Deviation 2.5258
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Total bilirubin, Day 14	-0.611 umol/L Standard Deviation 2.2851	-0.855 umol/L Standard Deviation 0.9366	-0.570 umol/L Standard Deviation 4.1418	0.285 umol/L Standard Deviation 2.5082
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Total bilirubin, Day 28	0.132 umol/L Standard Deviation 3.1578	-0.855 umol/L Standard Deviation 5.1584	-0.000 umol/L Standard Deviation 3.2445	0.998 umol/L Standard Deviation 2.2424
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Total bilirubin, Day 42	0.263 umol/L Standard Deviation 2.6898	-0.285 umol/L Standard Deviation 2.9453	-1.425 umol/L Standard Deviation 2.9453	-0.428 umol/L Standard Deviation 1.6507
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Creatinine, Day 7	3.0 umol/L Standard Deviation 4.10	6.9 umol/L Standard Deviation 5.60	4.6 umol/L Standard Deviation 6.41	3.4 umol/L Standard Deviation 4.47
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Creatinine, Day 14	4.2 umol/L Standard Deviation 5.61	5.7 umol/L Standard Deviation 8.21	-0.1 umol/L Standard Deviation 3.85	4.6 umol/L Standard Deviation 6.48
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Creatinine, Day 28	2.0 umol/L Standard Deviation 4.99	4.9 umol/L Standard Deviation 7.88	1.9 umol/L Standard Deviation 6.38	8.2 umol/L Standard Deviation 11.05
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C Creatinine, Day 42	-2.4 umol/L Standard Deviation 7.48	0.6 umol/L Standard Deviation 3.98	-1.0 umol/L Standard Deviation 3.60	-0.8 umol/L Standard Deviation 5.52

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Albumin, Day 14	0.4 g/L Standard Deviation 1.96	—	2.0 g/L Standard Deviation 1.83	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Albumin, Day 28	0.4 g/L Standard Deviation 1.07	—	2.5 g/L Standard Deviation 2.89	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Albumin, Day 42	0.0 g/L Standard Deviation 2.36	—	2.5 g/L Standard Deviation 2.08	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Total protein, Day 7	-2.1 g/L Standard Deviation 3.24	—	-0.8 g/L Standard Deviation 3.77	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Albumin, Day 7	-0.3 g/L Standard Deviation 1.90	—	0.0 g/L Standard Deviation 2.45	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Total protein, Day 14	-1.2 g/L Standard Deviation 4.00	—	-0.3 g/L Standard Deviation 2.06	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Total protein, Day 28	-2.2 g/L Standard Deviation 2.74	—	1.0 g/L Standard Deviation 2.45	—
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A Total protein, Day 42	-3.1 g/L Standard Deviation 4.25	—	0.8 g/L Standard Deviation 2.06	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Albumin, Day 7	3.1 g/L Standard Deviation 2.11	1.3 g/L Standard Deviation 2.07	2.0 g/L Standard Deviation 2.00	0.5 g/L Standard Deviation 1.88
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Albumin, Day 14	2.6 g/L Standard Deviation 2.17	0.8 g/L Standard Deviation 2.79	2.7 g/L Standard Deviation 3.01	1.6 g/L Standard Deviation 3.15
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Albumin, Day 28	2.8 g/L Standard Deviation 2.54	2.3 g/L Standard Deviation 1.97	1.8 g/L Standard Deviation 1.94	1.9 g/L Standard Deviation 2.71
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Albumin, Day 42	0.4 g/L Standard Deviation 2.02	-0.8 g/L Standard Deviation 1.94	0.0 g/L Standard Deviation 1.90	-1.3 g/L Standard Deviation 2.23
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Total protein, Day 7	2.9 g/L Standard Deviation 2.51	1.0 g/L Standard Deviation 4.15	3.0 g/L Standard Deviation 3.03	1.1 g/L Standard Deviation 3.12
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Total protein, Day 14	2.7 g/L Standard Deviation 3.67	1.7 g/L Standard Deviation 4.72	4.0 g/L Standard Deviation 5.10	2.2 g/L Standard Deviation 4.41
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Total protein, Day 28	3.2 g/L Standard Deviation 3.65	2.8 g/L Standard Deviation 4.17	3.2 g/L Standard Deviation 4.17	3.1 g/L Standard Deviation 4.03
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C Total protein, Day 42	-0.6 g/L Standard Deviation 2.79	-0.7 g/L Standard Deviation 3.08	0.5 g/L Standard Deviation 1.38	-1.5 g/L Standard Deviation 3.45

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A Day 7	12.516 Picomoles (pmol)/L Standard Deviation 28.0792	—	-1.256 Picomoles (pmol)/L Standard Deviation 26.7142	—
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A Day 14	1.973 Picomoles (pmol)/L Standard Deviation 13.8798	—	8.072 Picomoles (pmol)/L Standard Deviation 32.6673	—
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A Day 28	8.969 Picomoles (pmol)/L Standard Deviation 42.2377	—	-11.659 Picomoles (pmol)/L Standard Deviation 16.5012	—
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A Day 42	-13.735 Picomoles (pmol)/L Standard Deviation 11.7418	—	-22.721 Picomoles (pmol)/L Standard Deviation 17.5213	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C Day 7	-20.05 pmol/L Standard Deviation 90.341	45.11 pmol/L Standard Deviation 44.635	-20.21 pmol/L Standard Deviation 33.619	-29.59 pmol/L Standard Deviation 41.312
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C Day 14	-9.62 pmol/L Standard Deviation 62.083	-79.39 pmol/L Standard Deviation 33.851	-21.65 pmol/L Standard Deviation 61.873	-41.14 pmol/L Standard Deviation 67.791
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C Day 28	-35.18 pmol/L Standard Deviation 76.905	34.28 pmol/L Standard Deviation 70.064	-53.41 pmol/L Standard Deviation 48.574	-7.22 pmol/L Standard Deviation 39.675
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C Day 42	-8.12 pmol/L Standard Deviation 48.862	34.28 pmol/L Standard Deviation 36.025	-12.99 pmol/L Standard Deviation 40.953	35.28 pmol/L Standard Deviation 61.179

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study Amylase, Day 42	9.2 Units (U)/L Standard Deviation 29.49	—	6.0 Units (U)/L Standard Deviation 10.90	—
Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study Lipase, Day 42	18.8 Units (U)/L Standard Deviation 71.07	—	7.5 Units (U)/L Standard Deviation 21.25	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=8 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=4 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=5 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=10 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C	-0.009 Ratio Standard Deviation 0.0164	0.002 Ratio Standard Deviation 0.0126	-0.018 Ratio Standard Deviation 0.0110	-0.001 Ratio Standard Deviation 0.0173

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C Total thyroxine	1.0891 Nanomoles (nmol)/L Standard Deviation 6.62201	-5.1478 Nanomoles (nmol)/L Standard Deviation 7.09618	0.8578 Nanomoles (nmol)/L Standard Deviation 7.70771	-2.3597 Nanomoles (nmol)/L Standard Deviation 8.19189
Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C Total T3	0.1 Nanomoles (nmol)/L Standard Deviation 0.31	-0.2 Nanomoles (nmol)/L Standard Deviation 0.15	-0.3 Nanomoles (nmol)/L Standard Deviation NA Only one participant was analyzed for this arm at this time point.	-0.2 Nanomoles (nmol)/L Standard Deviation 0.16

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C Day 7	-5.790 Milliunits (mu/L) Standard Deviation NA Only one participant was analyzed for this arm at this time point.	—	—	—
Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C Day 42	-0.067 Milliunits (mu/L) Standard Deviation 0.2826	-0.187 Milliunits (mu/L) Standard Deviation 0.8308	0.137 Milliunits (mu/L) Standard Deviation 0.5036	0.149 Milliunits (mu/L) Standard Deviation 0.3342

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Basophils, Day 7	0.00 Giga cells (GI)/L Standard Deviation 0.000	—	0.00 Giga cells (GI)/L Standard Deviation 0.000	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Basophils, Day 14	0.01 Giga cells (GI)/L Standard Deviation 0.030	—	-0.03 Giga cells (GI)/L Standard Deviation 0.050	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Basophils, Day 28	0.00 Giga cells (GI)/L Standard Deviation 0.000	—	0.00 Giga cells (GI)/L Standard Deviation 0.000	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Basophils, Day 42	0.00 Giga cells (GI)/L Standard Deviation 0.000	—	0.00 Giga cells (GI)/L Standard Deviation 0.000	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Eosinophils, Day 7	-0.03 Giga cells (GI)/L Standard Deviation 0.065	—	-0.03 Giga cells (GI)/L Standard Deviation 0.050	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Eosinophils, Day 14	0.00 Giga cells (GI)/L Standard Deviation 0.063	—	-0.03 Giga cells (GI)/L Standard Deviation 0.050	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Eosinophils, Day 28	0.00 Giga cells (GI)/L Standard Deviation 0.067	—	0.10 Giga cells (GI)/L Standard Deviation 0.141	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Eosinophils, Day 42	0.00 Giga cells (GI)/L Standard Deviation 0.094	—	0.03 Giga cells (GI)/L Standard Deviation 0.050	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Lymphocytes, Day 7	-0.01 Giga cells (GI)/L Standard Deviation 0.644	—	-0.22 Giga cells (GI)/L Standard Deviation 0.287	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Lymphocytes, Day 14	-0.06 Giga cells (GI)/L Standard Deviation 0.448	—	-0.22 Giga cells (GI)/L Standard Deviation 0.050	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Lymphocytes, Day 28	-0.32 Giga cells (GI)/L Standard Deviation 0.496	—	-0.23 Giga cells (GI)/L Standard Deviation 0.189	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Lymphocytes, Day 42	0.05 Giga cells (GI)/L Standard Deviation 0.264	—	0.15 Giga cells (GI)/L Standard Deviation 0.520	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Monocytes, Day 7	-0.05 Giga cells (GI)/L Standard Deviation 0.104	—	-0.08 Giga cells (GI)/L Standard Deviation 0.126	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Monocytes, Day 14	-0.05 Giga cells (GI)/L Standard Deviation 0.069	—	-0.10 Giga cells (GI)/L Standard Deviation 0.000	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Monocytes, Day 28	0.01 Giga cells (GI)/L Standard Deviation 0.120	—	-0.05 Giga cells (GI)/L Standard Deviation 0.058	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Monocytes, Day 42	-0.06 Giga cells (GI)/L Standard Deviation 0.052	—	-0.05 Giga cells (GI)/L Standard Deviation 0.129	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Total Neutrophils, Day 7	0.02 Giga cells (GI)/L Standard Deviation 0.852	—	0.15 Giga cells (GI)/L Standard Deviation 0.947	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Total Neutrophils, Day 14	-0.13 Giga cells (GI)/L Standard Deviation 0.583	—	0.50 Giga cells (GI)/L Standard Deviation 0.990	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Total Neutrophils, Day 28	0.14 Giga cells (GI)/L Standard Deviation 0.841	—	-0.32 Giga cells (GI)/L Standard Deviation 0.465	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Total Neutrophils, Day 42	-0.01 Giga cells (GI)/L Standard Deviation 0.743	—	0.48 Giga cells (GI)/L Standard Deviation 0.556	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Platelet count, Day 7	-1.9 Giga cells (GI)/L Standard Deviation 16.65	—	-4.8 Giga cells (GI)/L Standard Deviation 26.08	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Platelet count, Day 14	3.8 Giga cells (GI)/L Standard Deviation 16.30	—	-14.0 Giga cells (GI)/L Standard Deviation 45.91	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Platelet count, Day 28	9.7 Giga cells (GI)/L Standard Deviation 29.04	—	-11.5 Giga cells (GI)/L Standard Deviation 51.98	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A Platelet count, Day 42	3.1 Giga cells (GI)/L Standard Deviation 25.18	—	-8.8 Giga cells (GI)/L Standard Deviation 17.37	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A WBC count, Day 7	-0.11 Giga cells (GI)/L Standard Deviation 1.118	—	-0.15 Giga cells (GI)/L Standard Deviation 1.310	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A WBC count, Day 14	-0.15 Giga cells (GI)/L Standard Deviation 0.715	—	0.18 Giga cells (GI)/L Standard Deviation 0.964	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A WBC count, Day 28	-0.16 Giga cells (GI)/L Standard Deviation 1.047	—	-0.50 Giga cells (GI)/L Standard Deviation 0.490	—
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A WBC count, Day 42	-0.01 Giga cells (GI)/L Standard Deviation 0.984	—	0.65 Giga cells (GI)/L Standard Deviation 0.988	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Basophils, Day 7	0.0047 GI/L Standard Deviation 0.01481	0.0047 GI/L Standard Deviation 0.00650	0.0270 GI/L Standard Deviation 0.03653	-0.0078 GI/L Standard Deviation 0.01673
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Basophils, Day 14	0.0041 GI/L Standard Deviation 0.01653	-0.0015 GI/L Standard Deviation 0.01195	0.0037 GI/L Standard Deviation 0.01122	-0.0066 GI/L Standard Deviation 0.01893
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Basophils, Day 28	0.0050 GI/L Standard Deviation 0.01755	-0.0065 GI/L Standard Deviation 0.04654	-0.0002 GI/L Standard Deviation 0.01418	-0.0068 GI/L Standard Deviation 0.02566
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Basophils, Day 42	0.0019 GI/L Standard Deviation 0.01499	-0.0190 GI/L Standard Deviation 0.04076	0.0098 GI/L Standard Deviation 0.00895	-0.0122 GI/L Standard Deviation 0.02336
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Eosinophils, Day 7	0.04 GI/L Standard Deviation 0.088	-0.01 GI/L Standard Deviation 0.055	0.02 GI/L Standard Deviation 0.040	-0.03 GI/L Standard Deviation 0.054
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Eosinophils, Day 14	0.03 GI/L Standard Deviation 0.086	-0.02 GI/L Standard Deviation 0.043	0.01 GI/L Standard Deviation 0.032	-0.00 GI/L Standard Deviation 0.044
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Eosinophils, Day 28	0.02 GI/L Standard Deviation 0.083	0.01 GI/L Standard Deviation 0.067	0.01 GI/L Standard Deviation 0.049	-0.00 GI/L Standard Deviation 0.079
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Eosinophils, Day 42	0.06 GI/L Standard Deviation 0.128	-0.02 GI/L Standard Deviation 0.041	0.01 GI/L Standard Deviation 0.045	-0.01 GI/L Standard Deviation 0.044
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Lymphocytes, Day 7	0.11 GI/L Standard Deviation 0.304	0.09 GI/L Standard Deviation 0.253	0.31 GI/L Standard Deviation 0.333	0.14 GI/L Standard Deviation 0.511
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Lymphocytes, Day 14	0.04 GI/L Standard Deviation 0.295	0.08 GI/L Standard Deviation 0.280	0.18 GI/L Standard Deviation 0.275	0.18 GI/L Standard Deviation 0.371
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Lymphocytes, Day 28	0.05 GI/L Standard Deviation 0.631	0.05 GI/L Standard Deviation 0.317	0.08 GI/L Standard Deviation 0.300	0.25 GI/L Standard Deviation 0.594
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Lymphocytes, Day 42	-0.11 GI/L Standard Deviation 0.228	-0.11 GI/L Standard Deviation 0.307	0.02 GI/L Standard Deviation 0.158	-0.07 GI/L Standard Deviation 0.364
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Monocytes, Day 7	-0.01 GI/L Standard Deviation 0.100	0.01 GI/L Standard Deviation 0.149	0.04 GI/L Standard Deviation 0.109	0.00 GI/L Standard Deviation 0.115
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Monocytes, Day 14	-0.04 GI/L Standard Deviation 0.122	0.06 GI/L Standard Deviation 0.125	-0.05 GI/L Standard Deviation 0.125	0.06 GI/L Standard Deviation 0.096
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Monocytes, Day 28	-0.03 GI/L Standard Deviation 0.080	0.06 GI/L Standard Deviation 0.099	0.03 GI/L Standard Deviation 0.147	0.03 GI/L Standard Deviation 0.132
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Monocytes, Day 42	-0.06 GI/L Standard Deviation 0.120	-0.00 GI/L Standard Deviation 0.087	0.00 GI/L Standard Deviation 0.100	-0.03 GI/L Standard Deviation 0.074
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Total Neutrophils, Day 7	-0.13 GI/L Standard Deviation 0.666	-0.54 GI/L Standard Deviation 0.500	0.27 GI/L Standard Deviation 0.431	0.38 GI/L Standard Deviation 0.786
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Total Neutrophils, Day 14	-0.19 GI/L Standard Deviation 0.722	-0.27 GI/L Standard Deviation 0.591	0.38 GI/L Standard Deviation 0.932	0.64 GI/L Standard Deviation 0.876
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Total Neutrophils, Day 28	-0.17 GI/L Standard Deviation 0.778	-0.48 GI/L Standard Deviation 1.097	-0.01 GI/L Standard Deviation 0.608	0.36 GI/L Standard Deviation 1.048
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Total Neutrophils, Day 42	-0.14 GI/L Standard Deviation 0.561	-0.50 GI/L Standard Deviation 0.845	-0.24 GI/L Standard Deviation 0.404	-0.10 GI/L Standard Deviation 0.645
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Platelet count, Day 7	8.9 GI/L Standard Deviation 18.10	5.0 GI/L Standard Deviation 20.82	18.3 GI/L Standard Deviation 24.21	5.8 GI/L Standard Deviation 21.36
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Platelet count, Day 14	7.0 GI/L Standard Deviation 11.02	1.2 GI/L Standard Deviation 31.94	12.8 GI/L Standard Deviation 29.31	12.9 GI/L Standard Deviation 15.97
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Platelet count, Day 28	10.8 GI/L Standard Deviation 21.90	0.5 GI/L Standard Deviation 34.01	4.5 GI/L Standard Deviation 23.87	10.4 GI/L Standard Deviation 16.91
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C Platelet count, Day 42	-13.2 GI/L Standard Deviation 30.99	-13.8 GI/L Standard Deviation 41.97	-2.0 GI/L Standard Deviation 23.13	-15.3 GI/L Standard Deviation 28.56
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C WBC count, Day 7	-0.01 GI/L Standard Deviation 0.791	-0.43 GI/L Standard Deviation 0.900	0.65 GI/L Standard Deviation 0.582	0.48 GI/L Standard Deviation 1.099
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C WBC count, Day 14	-0.17 GI/L Standard Deviation 0.862	-0.13 GI/L Standard Deviation 0.933	0.52 GI/L Standard Deviation 0.997	0.88 GI/L Standard Deviation 1.131
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C WBC count, Day 28	-0.13 GI/L Standard Deviation 1.057	-0.35 GI/L Standard Deviation 1.414	0.08 GI/L Standard Deviation 0.728	0.63 GI/L Standard Deviation 1.643
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C WBC count, Day 42	-0.26 GI/L Standard Deviation 0.413	-0.62 GI/L Standard Deviation 1.130	-0.20 GI/L Standard Deviation 0.533	-0.22 GI/L Standard Deviation 0.824

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A MCHC, Day 42	9.0 g/L Standard Deviation 11.75	—	17.5 g/L Standard Deviation 7.19	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A Hemoglobin, Day 7	-2.0 g/L Standard Deviation 6.36	—	0.8 g/L Standard Deviation 2.06	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A Hemoglobin, Day 14	-0.9 g/L Standard Deviation 7.30	—	4.0 g/L Standard Deviation 4.24	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A Hemoglobin, Day 28	0.5 g/L Standard Deviation 3.84	—	11.3 g/L Standard Deviation 7.41	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A Hemoglobin, Day 42	0.9 g/L Standard Deviation 9.34	—	9.8 g/L Standard Deviation 7.37	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A MCHC, Day 7	5.4 g/L Standard Deviation 7.31	—	1.8 g/L Standard Deviation 2.99	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A MCHC, Day 14	0.0 g/L Standard Deviation 5.71	—	-0.5 g/L Standard Deviation 9.40	—
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A MCHC, Day 28	6.3 g/L Standard Deviation 6.02	—	8.5 g/L Standard Deviation 7.55	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C Hemoglobin, Day 7	-1.0 g/L Standard Deviation 4.67	-4.3 g/L Standard Deviation 5.85	0.2 g/L Standard Deviation 5.08	-3.4 g/L Standard Deviation 6.89
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C Hemoglobin, Day 14	-1.1 g/L Standard Deviation 6.50	1.7 g/L Standard Deviation 4.93	0.2 g/L Standard Deviation 9.66	-2.1 g/L Standard Deviation 13.10
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C Hemoglobin, Day 28	-1.1 g/L Standard Deviation 7.63	-1.2 g/L Standard Deviation 8.68	0.3 g/L Standard Deviation 3.98	-0.3 g/L Standard Deviation 8.70
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C Hemoglobin, Day 42	-0.8 g/L Standard Deviation 4.87	-2.8 g/L Standard Deviation 4.58	0.0 g/L Standard Deviation 2.97	-4.8 g/L Standard Deviation 5.83
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C MCHC, Day 7	-4.1 g/L Standard Deviation 5.40	-4.5 g/L Standard Deviation 2.74	-2.0 g/L Standard Deviation 4.82	-2.8 g/L Standard Deviation 4.97
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C MCHC, Day 14	-3.8 g/L Standard Deviation 5.28	-1.2 g/L Standard Deviation 3.54	2.0 g/L Standard Deviation 7.21	-2.6 g/L Standard Deviation 5.09
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C MCHC, Day 28	-1.9 g/L Standard Deviation 4.80	-2.0 g/L Standard Deviation 5.22	1.7 g/L Standard Deviation 7.15	-1.4 g/L Standard Deviation 3.53
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C MCHC, Day 42	0.2 g/L Standard Deviation 4.36	-0.2 g/L Standard Deviation 2.79	2.0 g/L Standard Deviation 6.16	0.8 g/L Standard Deviation 4.63

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A RBC count, Day 7	-0.116 Trillion cells (TI)/L Standard Deviation 0.1851	—	-0.008 Trillion cells (TI)/L Standard Deviation 0.1014	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A RBC count, Day 14	-0.084 Trillion cells (TI)/L Standard Deviation 0.2313	—	0.090 Trillion cells (TI)/L Standard Deviation 0.0337	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A RBC count, Day 28	-0.045 Trillion cells (TI)/L Standard Deviation 0.1516	—	0.258 Trillion cells (TI)/L Standard Deviation 0.1455	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A RBC count, Day 42	-0.115 Trillion cells (TI)/L Standard Deviation 0.2632	—	0.107 Trillion cells (TI)/L Standard Deviation 0.3192	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A Reticulocytes, Day 7	0.0014 Trillion cells (TI)/L Standard Deviation 0.01076	—	0.0115 Trillion cells (TI)/L Standard Deviation 0.00281	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A Reticulocytes, Day 14	-0.0017 Trillion cells (TI)/L Standard Deviation 0.01001	—	0.0077 Trillion cells (TI)/L Standard Deviation 0.00189	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A Reticulocytes, Day 28	0.0071 Trillion cells (TI)/L Standard Deviation 0.01522	—	0.0073 Trillion cells (TI)/L Standard Deviation 0.00151	—
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A Reticulocytes, Day 42	0.0044 Trillion cells (TI)/L Standard Deviation 0.01396	—	0.0022 Trillion cells (TI)/L Standard Deviation 0.00998	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C RBC count, Day 7	0.004 TI/L Standard Deviation 0.1536	-0.107 TI/L Standard Deviation 0.2013	0.018 TI/L Standard Deviation 0.1916	-0.085 TI/L Standard Deviation 0.2176
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C RBC count, Day 14	-0.011 TI/L Standard Deviation 0.2282	0.093 TI/L Standard Deviation 0.2399	-0.030 TI/L Standard Deviation 0.2999	-0.072 TI/L Standard Deviation 0.4808
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C RBC count, Day 28	-0.023 TI/L Standard Deviation 0.2500	0.020 TI/L Standard Deviation 0.3651	0.002 TI/L Standard Deviation 0.1229	-0.003 TI/L Standard Deviation 0.2871
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C RBC count, Day 42	-0.031 TI/L Standard Deviation 0.1445	-0.053 TI/L Standard Deviation 0.1978	0.032 TI/L Standard Deviation 0.0662	-0.168 TI/L Standard Deviation 0.1987
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C Reticulocytes, Day 7	-0.0003 TI/L Standard Deviation 0.01284	-0.0210 TI/L Standard Deviation 0.02605	0.0020 TI/L Standard Deviation 0.01123	-0.0015 TI/L Standard Deviation 0.02719
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C Reticulocytes, Day 14	0.0095 TI/L Standard Deviation 0.02126	-0.0286 TI/L Standard Deviation 0.02354	-0.0019 TI/L Standard Deviation 0.02127	0.0147 TI/L Standard Deviation 0.02091
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C Reticulocytes, Day 28	0.0035 TI/L Standard Deviation 0.01697	-0.0304 TI/L Standard Deviation 0.01024	0.0029 TI/L Standard Deviation 0.01673	-0.0052 TI/L Standard Deviation 0.01674
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C Reticulocytes, Day 42	0.0096 TI/L Standard Deviation 0.01916	-0.0200 TI/L Standard Deviation 0.03679	0.0062 TI/L Standard Deviation 0.01283	-0.0042 TI/L Standard Deviation 0.02667

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A Day 7	-0.0128 Ratio Standard Deviation 0.01836	—	0.0000 Ratio Standard Deviation 0.00365	—
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A Day 14	-0.0026 Ratio Standard Deviation 0.01975	—	0.0128 Ratio Standard Deviation 0.00943	—
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A Day 28	-0.0066 Ratio Standard Deviation 0.01127	—	0.0228 Ratio Standard Deviation 0.01921	—
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A Day 42	-0.0089 Ratio Standard Deviation 0.02614	—	0.0060 Ratio Standard Deviation 0.02780	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C Day 7	0.0019 Ratio Standard Deviation 0.01645	-0.0082 Ratio Standard Deviation 0.01837	0.0032 Ratio Standard Deviation 0.01240	-0.0072 Ratio Standard Deviation 0.02007
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C Day 14	0.0011 Ratio Standard Deviation 0.02030	0.0057 Ratio Standard Deviation 0.01628	-0.0028 Ratio Standard Deviation 0.02218	-0.0036 Ratio Standard Deviation 0.03707
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C Day 28	-0.0003 Ratio Standard Deviation 0.02237	-0.0010 Ratio Standard Deviation 0.02832	-0.0003 Ratio Standard Deviation 0.00900	0.0003 Ratio Standard Deviation 0.02786
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C Day 42	-0.0025 Ratio Standard Deviation 0.01509	-0.0087 Ratio Standard Deviation 0.01154	-0.0022 Ratio Standard Deviation 0.01032	-0.0159 Ratio Standard Deviation 0.01827

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A Day 7	0.31 Picograms Standard Deviation 0.589	—	0.25 Picograms Standard Deviation 0.420	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A Day 14	0.32 Picograms Standard Deviation 0.453	—	0.27 Picograms Standard Deviation 0.881	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A Day 28	0.37 Picograms Standard Deviation 0.427	—	0.70 Picograms Standard Deviation 0.816	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A Day 42	0.89 Picograms Standard Deviation 0.924	—	1.40 Picograms Standard Deviation 0.841	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C Day 7	-0.21 Picograms Standard Deviation 0.315	-0.23 Picograms Standard Deviation 0.314	-0.02 Picograms Standard Deviation 0.160	-0.18 Picograms Standard Deviation 0.434
Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C Day 14	-0.10 Picograms Standard Deviation 0.476	-0.25 Picograms Standard Deviation 0.689	0.18 Picograms Standard Deviation 0.319	0.03 Picograms Standard Deviation 0.454
Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C Day 28	0.01 Picograms Standard Deviation 0.487	-0.20 Picograms Standard Deviation 0.410	0.17 Picograms Standard Deviation 0.484	-0.08 Picograms Standard Deviation 0.343
Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C Day 42	0.08 Picograms Standard Deviation 0.668	-0.28 Picograms Standard Deviation 0.500	-0.12 Picograms Standard Deviation 0.412	0.02 Picograms Standard Deviation 0.333

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A Day 7	-0.55 Femtoliters Standard Deviation 0.792	—	0.15 Femtoliters Standard Deviation 1.323	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A Day 14	0.95 Femtoliters Standard Deviation 0.682	—	0.85 Femtoliters Standard Deviation 1.348	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A Day 28	-0.62 Femtoliters Standard Deviation 1.105	—	-0.30 Femtoliters Standard Deviation 1.393	—
Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A Day 42	0.35 Femtoliters Standard Deviation 1.866	—	-0.90 Femtoliters Standard Deviation 1.219	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C Day 28	0.55 Femtoliters Standard Deviation 1.381	-0.18 Femtoliters Standard Deviation 1.465	0.05 Femtoliters Standard Deviation 0.967	0.17 Femtoliters Standard Deviation 1.303
Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C Day 7	0.39 Femtoliters Standard Deviation 1.296	0.40 Femtoliters Standard Deviation 0.443	0.35 Femtoliters Standard Deviation 1.067	0.25 Femtoliters Standard Deviation 1.119
Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C Day 14	0.54 Femtoliters Standard Deviation 1.134	-0.47 Femtoliters Standard Deviation 1.544	0.02 Femtoliters Standard Deviation 0.659	0.76 Femtoliters Standard Deviation 1.925
Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C Day 42	0.07 Femtoliters Standard Deviation 1.768	-0.78 Femtoliters Standard Deviation 1.468	-0.90 Femtoliters Standard Deviation 1.279	-0.27 Femtoliters Standard Deviation 1.263

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population.

The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as rare, trace, +1, 2+, RBC's and WBC's as \<1, 1, 2, 3 and 4. Protein concentration ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. Trace was the highest concentration for occult blood. Bacteria concentration ranged from rare to moderate, where rare indicated lowest concentration and moderate indicated highest concentration. Ketones ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. RBC and WBC ranged from \<1 to 4, where \<1 indicated lowest concentration and 4 indicated highest concentration. Highest concentration indicated worse outcome.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, Trace, Day 1	3 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, Trace, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, Trace, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, Trace, Day 28	4 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Protein, Trace, Day 42	2 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Bacteria, Rare, Day 1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Bacteria, Rare, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Bacteria, Moderate, Day 42	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Occult blood, Trace, Day 1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Occult blood, Trace, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Occult blood, Trace, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Ketones, 1+, Day 1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Ketones, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Ketones, Trace, Day 14	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Ketones, Trace, Day 28	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A Ketones, Trace, Day 42	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 1, Day 1	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 3, Day 1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, <1, Day 1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 1, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, <1, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 2, Day 14	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, <1, Day 14	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 1, Day 28	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, <1, Day 28	2 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 1, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, 2, Day 42	0 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A RBC's, <1, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 1, Day 1	2 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, <1, Day 1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 1, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, <1, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 2, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, <1, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 1, Day 28	0 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, <1, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 1, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 2, Day 42	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A WBC's, 4, Day 42	1 Participants	—	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as few, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, and 20-40. Few was the highest concentration of bacteria. Occult blood ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Epithelial cell ranged from 0-5 to 10-20, 0-5 indicated lowest and 10-20 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-5 was highest concentration for hyaline casts. Ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. RBC and WBC ranged from 0-3 to 20-40, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Bacteria, Few, Day -1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Occult Blood, 1+, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Occult Blood, Trace, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Occult Blood, Trace, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Epithelial Cells, 10-20, Day -1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Epithelial Cells, 0-5, Day 7	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Epithelial Cells, 6-10, Day 7	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Epithelial Cells, 0-5, Day 14	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Epithelial Cells, 0-5, Day 42	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 1+, Day -1	4 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 3+, Day -1	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, Trace, Day -1	1 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 3+, Day 7	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, Trace, Day 7	3 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 1+, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 2+, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 3+, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, Trace, Day 14	3 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 1+, Day 28	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 2+, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 3+, Day 28	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, Trace, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 1+, Day 42	0 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 2+, Day 42	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, 3+, Day 42	3 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Glucose, Trace, Day 42	3 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Hyaline Casts, 0-5, Day 14	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Ketones, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Ketones, Trace, Day 14	1 Participants	—	2 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B Ketones, Trace, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B RBC's, 0-3, Day-1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B RBC's, 0-3, Day 7	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B RBC's, 0-3, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B RBC's, 0-3, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B RBC's, 0-3, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 20-40, Day -1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 0-5, Day 7	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 6-10, Day 7	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 0-5, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 0-5, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B WBC's, 0-5, Day 42	1 Participants	—	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population.

The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. The participants were categorized as few, many, moderate, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, 20-40, 40-60. Protein and ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Bacteria and uric acid crystals ranged from few to moderate, few indicated lowest and moderate indicated highest concentration. Trace was the highest concentration of occult blood. Epithelial cells ranged from 0-5 to \>10, 0-5 indicated lowest and \>10 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-1 was highest concentration for hyaline casts. RBC and WBC ranged from 0-3 to 40-60, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Protein, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Protein, Trace, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Protein, Trace, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Protein, 1+, Day 28	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Few, Day -1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Many, Day -1	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Few, Day 7	4 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Many, Day 7	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Many, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Moderate, Day 14	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Few, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Many, Day 28	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Many, Day 42	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Bacteria, Moderate, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Occult Blood, Trace, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-10, Day -1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-10, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-5, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 6-10, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-5, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, >10, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-10, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Epithelial Cells, 0-10, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 1+, Day -1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 2+, Day -1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 3+, Day -1	6 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 1+, Day 7	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 2+, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 3+, Day 7	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, Trace, Day 7	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 1+, Day 14	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 3+, Day 14	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, Trace, Day 14	4 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 2+, Day 28	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 3+, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, Trace, Day 28	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 1+, Day 42	2 Participants	—	3 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 2+, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, 3+, Day 42	4 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Glucose, Trace, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Hyaline Casts, 0-1, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Ketones, 1+, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Ketones, Trace, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Ketones, Trace, Day 14	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Ketones, Trace, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C RBC's, 0-3, Day -1	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C RBC's, 0-3, Day 7	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C RBC's, 0-3, Day 14	2 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C RBC's, 0-3, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C RBC's, 0-3, Day 42	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Uric acid crystals, Moderate, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C Uric acid crystals, Few, Day 14	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 0-5, Day -1	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 0-5, Day 7	3 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 6-10, Day 7	1 Participants	—	0 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 0-5, Day 14	2 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 0-5, Day 28	1 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 40-60, Day 28	0 Participants	—	1 Participants	—
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C WBC's, 6-10, Day 42	1 Participants	—	1 Participants	—

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Da y 1, Day 7, Day 14, Day 28 and Day 42.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A Day 1	1.0175 Ratio Standard Deviation 0.00794	—	1.0193 Ratio Standard Deviation 0.00903	—
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A Day 7	1.0165 Ratio Standard Deviation 0.00887	—	1.0133 Ratio Standard Deviation 0.00685	—
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A Day 14	1.0152 Ratio Standard Deviation 0.00752	—	1.0153 Ratio Standard Deviation 0.00591	—
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A Day 28	1.0122 Ratio Standard Deviation 0.00983	—	1.0125 Ratio Standard Deviation 0.00705	—
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A Day 42	1.0161 Ratio Standard Deviation 0.00827	—	1.0155 Ratio Standard Deviation 0.00759	—

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C Day -1	1.0174 Ratio Standard Deviation 0.00482	1.0172 Ratio Standard Deviation 0.00627	1.0168 Ratio Standard Deviation 0.00773	1.0187 Ratio Standard Deviation 0.00796
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C Day 7	1.0191 Ratio Standard Deviation 0.00734	1.0197 Ratio Standard Deviation 0.00356	1.0208 Ratio Standard Deviation 0.00794	1.0208 Ratio Standard Deviation 0.00688
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C Day 14	1.0196 Ratio Standard Deviation 0.00812	1.0198 Ratio Standard Deviation 0.00382	1.0202 Ratio Standard Deviation 0.00861	1.0201 Ratio Standard Deviation 0.00629
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C Day 28	1.0239 Ratio Standard Deviation 0.00533	1.0213 Ratio Standard Deviation 0.00505	1.0232 Ratio Standard Deviation 0.00906	1.0213 Ratio Standard Deviation 0.00559
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C Day 42	1.0188 Ratio Standard Deviation 0.00910	1.0110 Ratio Standard Deviation 0.00544	1.0137 Ratio Standard Deviation 0.00535	1.0172 Ratio Standard Deviation 0.01021

PRIMARY outcome

Timeframe: up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day 1, Day 7, Day 14, Day 28 and Day 42.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Mean pH Values of Urine During the Double-blind Treatment Period of Part A Day 1	5.95 pH Standard Deviation 0.472	—	5.25 pH Standard Deviation 0.289	—
Mean pH Values of Urine During the Double-blind Treatment Period of Part A Day 7	5.86 pH Standard Deviation 0.745	—	5.88 pH Standard Deviation 0.854	—
Mean pH Values of Urine During the Double-blind Treatment Period of Part A Day 14	5.91 pH Standard Deviation 0.735	—	5.50 pH Standard Deviation 0.408	—
Mean pH Values of Urine During the Double-blind Treatment Period of Part A Day 28	6.05 pH Standard Deviation 0.832	—	6.13 pH Standard Deviation 1.031	—
Mean pH Values of Urine During the Double-blind Treatment Period of Part A Day 42	6.20 pH Standard Deviation 0.632	—	5.63 pH Standard Deviation 0.250	—

PRIMARY outcome

Timeframe: Up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day -1, Day 7, Day 14, Day 28 and Day 42.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C Day 28	5.96 pH Standard Deviation 0.477	5.67 pH Standard Deviation 0.408	5.75 pH Standard Deviation 0.418	5.63 pH Standard Deviation 0.311
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C Day -1	6.25 pH Standard Deviation 0.470	5.67 pH Standard Deviation 0.408	5.92 pH Standard Deviation 0.376	5.83 pH Standard Deviation 0.537
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C Day 7	5.89 pH Standard Deviation 0.350	5.83 pH Standard Deviation 0.816	5.83 pH Standard Deviation 0.683	5.42 pH Standard Deviation 0.359
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C Day 14	6.07 pH Standard Deviation 0.646	5.67 pH Standard Deviation 0.516	5.67 pH Standard Deviation 0.408	5.63 pH Standard Deviation 0.433
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C Day 42	6.08 pH Standard Deviation 0.449	5.58 pH Standard Deviation 0.376	6.00 pH Standard Deviation 0.316	5.58 pH Standard Deviation 0.417

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A SBP, Day 7	-4.0 Millimeters of mercury (mmHg) Standard Deviation 4.94	—	0.8 Millimeters of mercury (mmHg) Standard Deviation 11.70	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A SBP, Day 14	-3.9 Millimeters of mercury (mmHg) Standard Deviation 6.45	—	-0.5 Millimeters of mercury (mmHg) Standard Deviation 1.91	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A SBP, Day 28	-5.5 Millimeters of mercury (mmHg) Standard Deviation 7.55	—	-3.3 Millimeters of mercury (mmHg) Standard Deviation 6.45	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A SBP, Day 42	-7.5 Millimeters of mercury (mmHg) Standard Deviation 6.19	—	-1.0 Millimeters of mercury (mmHg) Standard Deviation 11.28	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A DBP, Day 7	-6.2 Millimeters of mercury (mmHg) Standard Deviation 4.12	—	-5.3 Millimeters of mercury (mmHg) Standard Deviation 4.50	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A DBP, Day 14	-5.0 Millimeters of mercury (mmHg) Standard Deviation 8.51	—	-1.8 Millimeters of mercury (mmHg) Standard Deviation 3.95	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A DBP, Day 28	-8.4 Millimeters of mercury (mmHg) Standard Deviation 5.72	—	-1.3 Millimeters of mercury (mmHg) Standard Deviation 5.56	—
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A DBP, Day 42	-6.4 Millimeters of mercury (mmHg) Standard Deviation 7.21	—	-0.8 Millimeters of mercury (mmHg) Standard Deviation 3.30	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C SBP, Day 7	2.0 mmHg Standard Deviation 11.05	3.2 mmHg Standard Deviation 6.94	1.6 mmHg Standard Deviation 11.11	-3.7 mmHg Standard Deviation 12.40
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C SBP, Day 14	3.6 mmHg Standard Deviation 8.52	3.2 mmHg Standard Deviation 9.28	5.6 mmHg Standard Deviation 9.70	-2.8 mmHg Standard Deviation 9.45
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C SBP, Day 28	0.2 mmHg Standard Deviation 9.51	4.5 mmHg Standard Deviation 13.29	-0.6 mmHg Standard Deviation 7.43	-7.4 mmHg Standard Deviation 9.62
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C SBP, Day 42	0.1 mmHg Standard Deviation 4.31	0.0 mmHg Standard Deviation 10.11	-2.6 mmHg Standard Deviation 6.18	-3.0 mmHg Standard Deviation 10.04
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C DBP, Day 7	0.4 mmHg Standard Deviation 4.88	0.9 mmHg Standard Deviation 4.53	-2.4 mmHg Standard Deviation 6.00	-0.8 mmHg Standard Deviation 5.71
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C DBP, Day 14	0.8 mmHg Standard Deviation 3.23	-0.8 mmHg Standard Deviation 2.42	2.1 mmHg Standard Deviation 6.87	-2.5 mmHg Standard Deviation 5.70
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C DBP, Day 28	0.4 mmHg Standard Deviation 5.33	-0.4 mmHg Standard Deviation 6.06	-3.3 mmHg Standard Deviation 3.96	-3.4 mmHg Standard Deviation 5.33
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C DBP, Day 42	0.8 mmHg Standard Deviation 4.32	1.1 mmHg Standard Deviation 4.35	-1.5 mmHg Standard Deviation 4.60	-3.2 mmHg Standard Deviation 5.30

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A Day 7	4.6 Beats per minute Standard Deviation 6.13	—	8.0 Beats per minute Standard Deviation 6.83	—
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A Day 14	0.6 Beats per minute Standard Deviation 6.75	—	6.3 Beats per minute Standard Deviation 7.27	—
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A Day 28	3.3 Beats per minute Standard Deviation 7.07	—	5.5 Beats per minute Standard Deviation 9.57	—
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A Day 42	-4.4 Beats per minute Standard Deviation 6.29	—	-1.3 Beats per minute Standard Deviation 7.37	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C Day 42	1.6 Beats per minute Standard Deviation 7.42	-3.2 Beats per minute Standard Deviation 5.85	-4.8 Beats per minute Standard Deviation 4.45	0.5 Beats per minute Standard Deviation 4.75
Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C Day 7	0.3 Beats per minute Standard Deviation 7.91	0.1 Beats per minute Standard Deviation 5.90	-3.6 Beats per minute Standard Deviation 6.37	1.6 Beats per minute Standard Deviation 6.81
Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C Day 14	0.4 Beats per minute Standard Deviation 7.65	0.8 Beats per minute Standard Deviation 7.71	-3.3 Beats per minute Standard Deviation 6.65	3.6 Beats per minute Standard Deviation 5.72
Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C Day 28	3.7 Beats per minute Standard Deviation 7.92	1.8 Beats per minute Standard Deviation 4.98	-7.8 Beats per minute Standard Deviation 7.37	1.5 Beats per minute Standard Deviation 8.70

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Follow-up (Day 56)

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QT duration corrected for HR by Fridericia's formula (QTcF) and QT duration corrected for HR by Bazett's formula (QTcB intervals. The assessments were done at Day 1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A PR Interval, Day 42	1.1 Milliseconds Standard Deviation 8.20	—	6.3 Milliseconds Standard Deviation 11.00	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A PR Interval, Follow-up	1.5 Milliseconds Standard Deviation 8.30	—	9.0 Milliseconds Standard Deviation 10.26	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QRS Duration, Day 42	-2.1 Milliseconds Standard Deviation 3.10	—	2.2 Milliseconds Standard Deviation 3.91	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QRS Duration, Follow-up	-0.7 Milliseconds Standard Deviation 6.40	—	3.9 Milliseconds Standard Deviation 6.05	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QT Interval, Day 42	16.4 Milliseconds Standard Deviation 20.32	—	10.8 Milliseconds Standard Deviation 13.52	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QT Interval, Follow-up	-10.2 Milliseconds Standard Deviation 12.81	—	0.3 Milliseconds Standard Deviation 19.29	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QTcB, Day 42	-3.3 Milliseconds Standard Deviation 14.89	—	8.2 Milliseconds Standard Deviation 14.56	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QTcB, Follow-up	6.3 Milliseconds Standard Deviation 15.65	—	6.9 Milliseconds Standard Deviation 9.50	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QTcF, Day 42	3.2 Milliseconds Standard Deviation 11.85	—	9.1 Milliseconds Standard Deviation 12.61	—
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A QTcF, Follow-up	0.7 Milliseconds Standard Deviation 11.34	—	4.8 Milliseconds Standard Deviation 7.81	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QTcB, QTcF and RR intervals. The assessments were done at Day -1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in ECG Intervals During Part B and C RR Interval, Follow-up	0.02 Milliseconds Standard Deviation 0.127	0.02 Milliseconds Standard Deviation 0.091	0.03 Milliseconds Standard Deviation 0.107	-0.01 Milliseconds Standard Deviation 0.088
Change From Baseline in ECG Intervals During Part B and C QTcB, Day 42	-1.51 Milliseconds Standard Deviation 14.358	0.43 Milliseconds Standard Deviation 13.099	-2.87 Milliseconds Standard Deviation 12.081	-4.23 Milliseconds Standard Deviation 11.896
Change From Baseline in ECG Intervals During Part B and C QTcB, Follow-up	-10.95 Milliseconds Standard Deviation 14.939	-3.20 Milliseconds Standard Deviation 15.699	-5.89 Milliseconds Standard Deviation 7.088	-2.14 Milliseconds Standard Deviation 17.641
Change From Baseline in ECG Intervals During Part B and C QTcF, Day 42	-1.49 Milliseconds Standard Deviation 11.971	1.22 Milliseconds Standard Deviation 7.799	1.17 Milliseconds Standard Deviation 9.777	-2.58 Milliseconds Standard Deviation 10.229
Change From Baseline in ECG Intervals During Part B and C PR Interval, Day 42	3.08 Milliseconds Standard Deviation 14.104	-6.44 Milliseconds Standard Deviation 8.334	5.56 Milliseconds Standard Deviation 6.206	-4.44 Milliseconds Standard Deviation 10.156
Change From Baseline in ECG Intervals During Part B and C PR Interval, Follow-up	-3.69 Milliseconds Standard Deviation 11.708	-3.11 Milliseconds Standard Deviation 5.652	-1.11 Milliseconds Standard Deviation 14.327	-6.28 Milliseconds Standard Deviation 13.676
Change From Baseline in ECG Intervals During Part B and C QRS Duration, Day 42	-2.62 Milliseconds Standard Deviation 3.049	0.11 Milliseconds Standard Deviation 4.204	0.78 Milliseconds Standard Deviation 3.897	-1.06 Milliseconds Standard Deviation 2.947
Change From Baseline in ECG Intervals During Part B and C QRS Duration, Follow-up	-1.69 Milliseconds Standard Deviation 5.985	0.78 Milliseconds Standard Deviation 1.760	0.11 Milliseconds Standard Deviation 2.903	0.11 Milliseconds Standard Deviation 3.421
Change From Baseline in ECG Intervals During Part B and C QT Interval, Day 42	-1.69 Milliseconds Standard Deviation 17.212	2.78 Milliseconds Standard Deviation 17.711	8.11 Milliseconds Standard Deviation 10.477	0.78 Milliseconds Standard Deviation 15.431
Change From Baseline in ECG Intervals During Part B and C QT Interval, Follow-up	-5.69 Milliseconds Standard Deviation 25.885	0.78 Milliseconds Standard Deviation 7.559	1.44 Milliseconds Standard Deviation 27.022	-5.56 Milliseconds Standard Deviation 17.220
Change From Baseline in ECG Intervals During Part B and C QTcF, Follow-up	-9.10 Milliseconds Standard Deviation 12.639	-1.78 Milliseconds Standard Deviation 9.340	-3.17 Milliseconds Standard Deviation 11.117	-3.50 Milliseconds Standard Deviation 13.849
Change From Baseline in ECG Intervals During Part B and C RR Interval, Day 42	-0.00 Milliseconds Standard Deviation 0.086	0.01 Milliseconds Standard Deviation 0.120	0.04 Milliseconds Standard Deviation 0.045	0.02 Milliseconds Standard Deviation 0.074

PRIMARY outcome

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14 and 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A Day 7	0.08 Scores on scale Standard Deviation 0.120	—	0.02 Scores on scale Standard Deviation 0.033	—
Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A Day 14	0.04 Scores on scale Standard Deviation 0.105	—	0.08 Scores on scale Standard Deviation 0.100	—
Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A Day 42	-0.02 Scores on scale Standard Deviation 0.071	—	0.02 Scores on scale Standard Deviation 0.033	—

PRIMARY outcome

Timeframe: Baseline (Day -2) up to Day 41

Population: All Subjects Population. Only those participants available at the specified time points were analyzed.

The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day -2. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14, 28 and 41) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C Day 7	-0.03 Scores on scale Standard Deviation 0.473	0.24 Scores on scale Standard Deviation 0.397	0.03 Scores on scale Standard Deviation 0.516	0.13 Scores on scale Standard Deviation 0.197
Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C Day 14	0.05 Scores on scale Standard Deviation 0.440	0.20 Scores on scale Standard Deviation 0.386	-0.09 Scores on scale Standard Deviation 0.167	0.28 Scores on scale Standard Deviation 0.366
Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C Day 28	0.03 Scores on scale Standard Deviation 0.428	0.14 Scores on scale Standard Deviation 0.281	-0.21 Scores on scale Standard Deviation 0.191	0.27 Scores on scale Standard Deviation 0.436
Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C Day 41	-0.12 Scores on scale Standard Deviation 0.290	0.02 Scores on scale Standard Deviation 0.091	-0.11 Scores on scale Standard Deviation 0.259	0.10 Scores on scale Standard Deviation 0.325

PRIMARY outcome

Timeframe: Baseline (Day -1 and Day 1) up to Day 42

Population: Pharmacodynamic (PD) Population comprised of all participants in the All Subjects Population who had Baseline and at least one post-Baseline assessment of the endpoint. Only those participants available at the specified time points were analyzed.

During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 7	0.20 Kilograms (kg) Standard Deviation 1.368	0.28 Kilograms (kg) Standard Deviation 0.579	-0.12 Kilograms (kg) Standard Deviation 0.938	0.47 Kilograms (kg) Standard Deviation 0.840
Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 14	0.05 Kilograms (kg) Standard Deviation 1.292	0.61 Kilograms (kg) Standard Deviation 1.009	0.37 Kilograms (kg) Standard Deviation 1.157	0.56 Kilograms (kg) Standard Deviation 0.779
Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 28	0.47 Kilograms (kg) Standard Deviation 1.627	0.52 Kilograms (kg) Standard Deviation 0.612	0.15 Kilograms (kg) Standard Deviation 1.161	0.27 Kilograms (kg) Standard Deviation 1.265
Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 42	-0.39 Kilograms (kg) Standard Deviation 1.687	-0.47 Kilograms (kg) Standard Deviation 1.104	-0.74 Kilograms (kg) Standard Deviation 1.020	0.42 Kilograms (kg) Standard Deviation 1.221

PRIMARY outcome

Timeframe: Baseline (Day -1 and Day 1) up to Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed.

During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. Percent change was calculated by multiplying the change from Baseline value with 100. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 7	0.18 Percent change Standard Deviation 1.521	0.36 Percent change Standard Deviation 0.719	-0.16 Percent change Standard Deviation 1.020	0.59 Percent change Standard Deviation 0.892
Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 14	-0.04 Percent change Standard Deviation 1.442	0.79 Percent change Standard Deviation 1.346	0.47 Percent change Standard Deviation 1.252	0.60 Percent change Standard Deviation 0.780
Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 28	0.39 Percent change Standard Deviation 1.792	0.66 Percent change Standard Deviation 0.813	0.25 Percent change Standard Deviation 1.264	0.30 Percent change Standard Deviation 1.371
Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C Day 42	-0.51 Percent change Standard Deviation 1.884	-0.53 Percent change Standard Deviation 1.504	-0.80 Percent change Standard Deviation 1.199	0.50 Percent change Standard Deviation 1.365

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed.

AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean glucose AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. Adjusted mean is reported as least square (LS) mean.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C AUC (0-4 hour)	-0.164 mmol/L Standard Error 0.390	1.194 mmol/L Standard Error 0.518	0.018 mmol/L Standard Error 0.583	0.341 mmol/L Standard Error 0.359
Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C AUC (0-24 hour)	-0.968 mmol/L Standard Error 0.278	1.376 mmol/L Standard Error 0.459	-0.613 mmol/L Standard Error 0.410	0.156 mmol/L Standard Error 0.316

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42 of Part B and C

Population: PD Population. Only those participants available at the specified time points were analyzed.

Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C	-0.230 mmol/L Standard Error 0.375	0.136 mmol/L Standard Error 0.520	-0.384 mmol/L Standard Error 0.556	-0.387 mmol/L Standard Error 0.351

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed.

Two fasting samples 5 minutes apart were taken for insulin. Baseline insulin level was the average of the 2 fasting samples. For insulin weighted mean AUC (0-4 hour) and weighted mean AUC (0-24 hour) was calculated for Baseline (Day -1) and end of treatment (Day 42). AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean insulin AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C Fasting Insulin	1.133 pmol/L Standard Deviation 20.2106	-11.946 pmol/L Standard Deviation 28.0383	-4.887 pmol/L Standard Deviation 16.5321	12.300 pmol/L Standard Deviation 45.8067
Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C Insulin Weighted Mean AUC 0-4 hour	14.589 pmol/L Standard Deviation 67.3782	57.887 pmol/L Standard Deviation 74.4685	69.635 pmol/L Standard Deviation 31.8542	10.322 pmol/L Standard Deviation 81.6157
Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C Insulin Weighted Mean AUC 0-24 hour	-13.905 pmol/L Standard Deviation 42.6248	22.740 pmol/L Standard Deviation 50.2234	1.626 pmol/L Standard Deviation 50.3186	17.134 pmol/L Standard Deviation 79.9432

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed.

Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C	-0.278 Percent of TL hemoglobin Standard Error 0.113	0.018 Percent of TL hemoglobin Standard Error 0.264	-0.214 Percent of TL hemoglobin Standard Error 0.167	-0.201 Percent of TL hemoglobin Standard Error 0.187

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed. Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

HOMA-IR was calculated from the Day -1 and Day 42 fasting glucose and insulin values using dataset generated from the HOMA-2 model. It contained the estimates for HOMA-% insulin sensitivity (S) for pairs of fasting glucose and fasting insulin values. Study data was merged with the HOMA dataset by glucose and insulin. HOMA-IR was calculated as 100/HOMA-%S. HOMA-IR was not determined for any values outside the ranges of plasma glucose 3.5 to 25.0 mmol/L (63 - 450 mg/dL) and plasma insulin 20 to 400 pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C	0.017 mU*mmol/L^2 Standard Deviation 0.7222	—	-0.150 mU*mmol/L^2 Standard Deviation 0.4970	—

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 42

Population: PD Population. Only those participants available at the specified time points were analyzed. Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

The matsuda index was calculated from the Day -1 and Day 42 glucose and insulin results as 10,000 divided by (fasting plasma glucose x fasting plasma insulin x mean glucose at 0-2 hour post-dose x mean insulin at 0-2 hour post dose)\^1/2, where glucose was measured in mmol/L and insulin in pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=13 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C	-0.602 DecilitermL/mgmU Standard Deviation 2.4187	—	-0.991 DecilitermL/mgmU Standard Deviation 0.6904	—

PRIMARY outcome

Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

Population: PD Population. Only those participants available at the specified time points were analyzed.

The assessments were done at Day -1, Day 7, Day 14, Day 28, Day 42 and Follow-up Visit. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline (Day 7, 14, 28, 42 and Follow-up visit) values.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 Participants Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin n=12 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C Day 7	0.285 mmol/L Standard Deviation 3.2948	0.879 mmol/L Standard Deviation 2.4090	-0.278 mmol/L Standard Deviation 1.3178	-1.665 mmol/L Standard Deviation 1.8607
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C Day 14	0.210 mmol/L Standard Deviation 2.0999	0.518 mmol/L Standard Deviation 2.0551	-0.093 mmol/L Standard Deviation 1.1748	-2.216 mmol/L Standard Deviation 2.4434
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C Day 28	-0.201 mmol/L Standard Deviation 2.3145	1.536 mmol/L Standard Deviation 2.7121	-0.111 mmol/L Standard Deviation 1.7135	-1.989 mmol/L Standard Deviation 2.7612
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C Day 42	-0.098 mmol/L Standard Deviation 2.2967	1.184 mmol/L Standard Deviation 0.6983	0.194 mmol/L Standard Deviation 1.0630	0.074 mmol/L Standard Deviation 1.6151
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C Follow-up	0.444 mmol/L Standard Deviation 3.0739	1.249 mmol/L Standard Deviation 1.9061	0.962 mmol/L Standard Deviation 1.9719	-1.226 mmol/L Standard Deviation 1.3623

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

Population: Liraglutide Pharmacokinetic (PK) Population in Part B. Only those participants available at specified time points were analyzed. Results from descriptive summary used Liraglutide PK Population. However, results of statistical analysis compared Day 42 to Day -1 PK in GSK2890457+Liraglutide group who were in the Liraglutide PK Population.

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post dose. The AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Liraglutide Pharmacokinetic (PK) Population in Part B comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for Liraglutide.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B Day -1	1268.65 Hour*nanograms/mL Geometric Coefficient of Variation 91.758	—	2210.15 Hour*nanograms/mL Geometric Coefficient of Variation 74.900	—
Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B Day 42	1265.92 Hour*nanograms/mL Geometric Coefficient of Variation 79.435	—	2505.23 Hour*nanograms/mL Geometric Coefficient of Variation 99.731	—

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

Population: Liraglutide PK Population in Part B. Only those participants available at the specified time points were analyzed. Results from descriptive summary used Liraglutide PK Population. However, results of statistical analysis compared Day 42 to Day -1 PK in GSK2890457+Liraglutide group who were in the Liraglutide PK Population.

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B Day -1	72.24 Nanograms/mL Geometric Coefficient of Variation 70.492	—	120.00 Nanograms/mL Geometric Coefficient of Variation 66.845	—
Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B Day 42	70.86 Nanograms/mL Geometric Coefficient of Variation 63.525	—	128.57 Nanograms/mL Geometric Coefficient of Variation 86.860	—

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

Population: Liraglutide PK Population in Part B. Only those participants available at the specified time points were analyzed.

Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=14 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=6 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B Day -1	8.00 Hours Interval 0.0 to 11.5	—	9.74 Hours Interval 2.0 to 11.5	—
Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B Day 42	9.98 Hours Interval 0.8 to 23.8	—	9.92 Hours Interval 2.1 to 11.5	—

SECONDARY outcome

Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

Population: Metformin PK Population in Part A. Only those participants available at specified time points were analyzed. The results from the descriptive summary used the PK Population. However, the results of the statistical analysis compared Day 42 to Day 1 PK only in the GSK2890457 group who were in the PK Population.

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The AUC (0-10 hour) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Metformin PK Population in Part A comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for metformin.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A Day 1	3402.6 Hour*nanograms/mL Geometric Coefficient of Variation 26.4	—	4346.8 Hour*nanograms/mL Geometric Coefficient of Variation 19.1	—
AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A Day 42	2231.7 Hour*nanograms/mL Geometric Coefficient of Variation 38.6	—	5081.9 Hour*nanograms/mL Geometric Coefficient of Variation 21.1	—

SECONDARY outcome

Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

Population: Metformin PK Population in Part A. Only those participants available at specified time points were analyzed. The results from the descriptive summary used the PK Population. However, the results of the statistical analysis compared Day 42 to Day 1 PK only in the GSK2890457 group who were in the PK Population.

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Cmax of Metformin During the Double-blind Treatment Period of Part A Day 1	576.2 Nanograms/mL Geometric Coefficient of Variation 24.4	—	681.8 Nanograms/mL Geometric Coefficient of Variation 19.0	—
Cmax of Metformin During the Double-blind Treatment Period of Part A Day 42	374.1 Nanograms/mL Geometric Coefficient of Variation 31.2	—	860.1 Nanograms/mL Geometric Coefficient of Variation 18.8	—

SECONDARY outcome

Timeframe: Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

Population: Metformin PK Population in Part A. Only those participants available at the specified time points were analyzed.

Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Tmax of Metformin During the Double-blind Treatment Period of Part A Day 1	2.000 Hours Interval 1.0 to 4.0	—	3.010 Hours Interval 2.0 to 4.03	—
Tmax of Metformin During the Double-blind Treatment Period of Part A Day 42	2.000 Hours Interval 2.0 to 5.5	—	4.000 Hours Interval 2.0 to 4.03	—

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Population: Metformin PK Population in Part C comprised of all participants in the All Subjects Population for whom a PK sample was obtained and analyzed for metformin. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The AUC 0-t was planned to be determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Population: Metformin PK Population in Part C. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Population: Metformin PK Population in Part C. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.

Outcome measures

Outcome data not reported

Adverse Events

Part A-Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A-GSK2890457

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Part B-Placebo+Liraglutide

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part B-GSK2890457+Liraglutide

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part C-Placebo+Metformin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part C-GSK2890457+Metformin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Part A-Placebo n=4 participants at risk Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID or 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) prior to breakfast (morning) and 10 g (2 unit) prior to dinner (evening). On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part A-GSK2890457 n=11 participants at risk Healthy participants received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, GSK2890457 was given in the evening.	Part B-Placebo+Liraglutide n=6 participants at risk Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with placebo.	Part B-GSK2890457+Liraglutide n=14 participants at risk Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin n=6 participants at risk Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part C-GSK2890457+Metformin n=12 participants at risk Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Gastrointestinal disorders Flatulence	50.0% 2/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	81.8% 9/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	45.5% 5/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Abdominal pain upper	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	18.2% 2/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	8.3% 1/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Faeces discoloured	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	27.3% 3/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	18.2% 2/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	16.7% 1/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	8.3% 1/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	18.2% 2/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Gastrointestinal motility disorder	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	18.2% 2/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Gastrointestinal sounds abnormal	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Change of bowel habit	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Constipation	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	16.7% 1/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Defaecation urgency	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Eructation	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Nausea	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	16.7% 1/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	8.3% 1/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	8.3% 1/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Infections and infestations Upper respiratory tract infection	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Infections and infestations Rhinitis	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Metabolism and nutrition disorders Increased appetite	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
General disorders Fatigue	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	9.1% 1/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
General disorders Injection site erythema	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
General disorders Injection site haemorrhage	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Immune system disorders Hypersensitivity	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Investigations Alanine aminotransferase increased	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	16.7% 1/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	16.7% 1/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Nervous system disorders Headache	25.0% 1/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Nervous system disorders Paraesthesia	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Nervous system disorders Sensory disturbance	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	7.1% 1/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Cardiac disorders Bundle branch block right	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Injury, poisoning and procedural complications Excoriation	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.
Psychiatric disorders Claustrophobia	0.00% 0/4 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/11 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/14 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	0.00% 0/6 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.	8.3% 1/12 • AEs were collected up to Follow-up (8 weeks). All Subjects Population was used.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALP, Day 7	-3.8 International unit per liter (IU/L) Standard Deviation 3.28	—	-6.0 International unit per liter (IU/L) Standard Deviation 5.83	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALP, Day 14	-1.4 International unit per liter (IU/L) Standard Deviation 5.30	—	-1.3 International unit per liter (IU/L) Standard Deviation 6.08	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALP, Day 28	-1.8 International unit per liter (IU/L) Standard Deviation 2.82	—	0.0 International unit per liter (IU/L) Standard Deviation 4.83	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALP, Day 42	-1.8 International unit per liter (IU/L) Standard Deviation 4.73	—	-1.0 International unit per liter (IU/L) Standard Deviation 3.37	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALT, Day 7	-4.1 International unit per liter (IU/L) Standard Deviation 6.74	—	5.5 International unit per liter (IU/L) Standard Deviation 10.15	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALT, Day 14	-4.4 International unit per liter (IU/L) Standard Deviation 8.27	—	1.3 International unit per liter (IU/L) Standard Deviation 2.99	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALT, Day 28	-8.2 International unit per liter (IU/L) Standard Deviation 10.76	—	2.0 International unit per liter (IU/L) Standard Deviation 5.48	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A ALT, Day 42	-7.7 International unit per liter (IU/L) Standard Deviation 9.31	—	5.3 International unit per liter (IU/L) Standard Deviation 17.37	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A AST, Day 7	-0.4 International unit per liter (IU/L) Standard Deviation 5.73	—	2.3 International unit per liter (IU/L) Standard Deviation 2.06	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A AST, Day 14	1.4 International unit per liter (IU/L) Standard Deviation 5.45	—	-2.3 International unit per liter (IU/L) Standard Deviation 3.40	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A AST, Day 28	-3.1 International unit per liter (IU/L) Standard Deviation 4.95	—	-0.8 International unit per liter (IU/L) Standard Deviation 3.10	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A AST, Day 42	-0.3 International unit per liter (IU/L) Standard Deviation 4.62	—	2.3 International unit per liter (IU/L) Standard Deviation 6.95	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A GGT, Day 7	-0.1 International unit per liter (IU/L) Standard Deviation 2.39	—	1.5 International unit per liter (IU/L) Standard Deviation 5.45	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A GGT, Day 14	-0.1 International unit per liter (IU/L) Standard Deviation 3.27	—	1.0 International unit per liter (IU/L) Standard Deviation 4.24	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A GGT, Day 28	-2.9 International unit per liter (IU/L) Standard Deviation 4.41	—	0.8 International unit per liter (IU/L) Standard Deviation 4.86	—
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A GGT, Day 42	-0.5 International unit per liter (IU/L) Standard Deviation 3.81	—	2.5 International unit per liter (IU/L) Standard Deviation 4.36	—

Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Calcium, Day 7	-0.023 Millimoles (mmol)/L Standard Deviation 0.0718	—	-0.025 Millimoles (mmol)/L Standard Deviation 0.1019	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Calcium, Day 14	-0.023 Millimoles (mmol)/L Standard Deviation 0.0875	—	0.056 Millimoles (mmol)/L Standard Deviation 0.0624	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Calcium, Day 28	-0.010 Millimoles (mmol)/L Standard Deviation 0.0554	—	0.056 Millimoles (mmol)/L Standard Deviation 0.0985	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Calcium, Day 42	-0.022 Millimoles (mmol)/L Standard Deviation 0.0729	—	0.050 Millimoles (mmol)/L Standard Deviation 0.0611	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Chloride, Day 7	1.2 Millimoles (mmol)/L Standard Deviation 1.89	—	0.8 Millimoles (mmol)/L Standard Deviation 2.50	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Chloride, Day 14	0.4 Millimoles (mmol)/L Standard Deviation 1.63	—	1.0 Millimoles (mmol)/L Standard Deviation 0.82	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Chloride, Day 28	0.5 Millimoles (mmol)/L Standard Deviation 2.12	—	-1.5 Millimoles (mmol)/L Standard Deviation 0.58	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Chloride, Day 42	0.4 Millimoles (mmol)/L Standard Deviation 2.12	—	-0.8 Millimoles (mmol)/L Standard Deviation 1.26	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Carbon dioxide/Bicarbonate, Day 7	-1.2 Millimoles (mmol)/L Standard Deviation 1.72	—	0.3 Millimoles (mmol)/L Standard Deviation 1.50	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Carbon dioxide/Bicarbonate, Day 14	-1.9 Millimoles (mmol)/L Standard Deviation 1.64	—	-1.0 Millimoles (mmol)/L Standard Deviation 2.16	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Carbon dioxide/Bicarbonate, Day 28	-1.2 Millimoles (mmol)/L Standard Deviation 1.75	—	-0.5 Millimoles (mmol)/L Standard Deviation 2.08	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Carbon dioxide/Bicarbonate, Day 42	-2.8 Millimoles (mmol)/L Standard Deviation 2.44	—	-2.5 Millimoles (mmol)/L Standard Deviation 2.08	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Glucose, Day 7	-0.1 Millimoles (mmol)/L Standard Deviation 0.35	—	-0.0 Millimoles (mmol)/L Standard Deviation 0.51	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Glucose, Day 14	-0.3 Millimoles (mmol)/L Standard Deviation 0.37	—	-0.0 Millimoles (mmol)/L Standard Deviation 0.44	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Glucose, Day 28	-0.2 Millimoles (mmol)/L Standard Deviation 0.33	—	-0.1 Millimoles (mmol)/L Standard Deviation 0.45	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Glucose, Day 42	-0.3 Millimoles (mmol)/L Standard Deviation 0.28	—	-0.2 Millimoles (mmol)/L Standard Deviation 0.22	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Potassium, Day 7	-0.15 Millimoles (mmol)/L Standard Deviation 0.491	—	0.15 Millimoles (mmol)/L Standard Deviation 0.387	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Potassium, Day 14	-0.15 Millimoles (mmol)/L Standard Deviation 0.406	—	0.20 Millimoles (mmol)/L Standard Deviation 0.804	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Potassium, Day 28	-0.13 Millimoles (mmol)/L Standard Deviation 0.419	—	-0.07 Millimoles (mmol)/L Standard Deviation 0.419	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Potassium, Day 42	-0.16 Millimoles (mmol)/L Standard Deviation 0.548	—	0.30 Millimoles (mmol)/L Standard Deviation 0.673	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Magnesium, Day 7	-0.0299 Millimoles (mmol)/L Standard Deviation 0.02658	—	-0.0206 Millimoles (mmol)/L Standard Deviation 0.05306	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Magnesium, Day 14	-0.0486 Millimoles (mmol)/L Standard Deviation 0.02478	—	-0.0617 Millimoles (mmol)/L Standard Deviation 0.07119	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Magnesium, Day 28	-0.0288 Millimoles (mmol)/L Standard Deviation 0.03384	—	-0.0411 Millimoles (mmol)/L Standard Deviation 0.05812	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Magnesium, Day 42	-0.0247 Millimoles (mmol)/L Standard Deviation 0.06484	—	-0.0308 Millimoles (mmol)/L Standard Deviation 0.02055	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Sodium, Day 7	0.8 Millimoles (mmol)/L Standard Deviation 1.60	—	0.3 Millimoles (mmol)/L Standard Deviation 2.99	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Sodium, Day 14	-0.2 Millimoles (mmol)/L Standard Deviation 1.78	—	-0.3 Millimoles (mmol)/L Standard Deviation 1.26	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Sodium, Day 28	1.9 Millimoles (mmol)/L Standard Deviation 2.23	—	1.0 Millimoles (mmol)/L Standard Deviation 3.37	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Sodium, Day 42	-0.6 Millimoles (mmol)/L Standard Deviation 1.65	—	-1.3 Millimoles (mmol)/L Standard Deviation 2.75	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Urea/BUN, Day 7	-0.325 Millimoles (mmol)/L Standard Deviation 0.7732	—	-0.179 Millimoles (mmol)/L Standard Deviation 1.4428	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Urea/BUN, Day 14	-0.746 Millimoles (mmol)/L Standard Deviation 0.6859	—	-0.268 Millimoles (mmol)/L Standard Deviation 1.1795	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Urea/BUN, Day 28	-0.643 Millimoles (mmol)/L Standard Deviation 1.1264	—	-0.536 Millimoles (mmol)/L Standard Deviation 1.6098	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Urea/BUN, Day 42	-0.678 Millimoles (mmol)/L Standard Deviation 0.7794	—	-0.625 Millimoles (mmol)/L Standard Deviation 2.1095	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Phosphorus inorganic, Day 7	-0.04 Millimoles (mmol)/L Standard Deviation 0.090	—	-0.07 Millimoles (mmol)/L Standard Deviation 0.165	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Phosphorus inorganic, Day 14	-0.05 Millimoles (mmol)/L Standard Deviation 0.071	—	-0.14 Millimoles (mmol)/L Standard Deviation 0.138	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Phosphorus inorganic, Day 28	-0.09 Millimoles (mmol)/L Standard Deviation 0.112	—	-0.02 Millimoles (mmol)/L Standard Deviation 0.107	—
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A Phosphorus inorganic, Day 42	-0.03 Millimoles (mmol)/L Standard Deviation 0.138	—	0.01 Millimoles (mmol)/L Standard Deviation 0.085	—

Measure	Part B-GSK2890457+Liraglutide n=11 Participants Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457.	Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID.	Part A-Placebo n=4 Participants Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening.	Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID.
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Direct bilirubin, Day 7	-0.311 Micromoles (umol)/L Standard Deviation 2.2709	—	0.000 Micromoles (umol)/L Standard Deviation 1.3962	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Direct bilirubin, Day 14	-0.466 Micromoles (umol)/L Standard Deviation 1.1058	—	0.428 Micromoles (umol)/L Standard Deviation 0.8550	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Direct bilirubin, Day 28	-0.855 Micromoles (umol)/L Standard Deviation 1.6618	—	-0.428 Micromoles (umol)/L Standard Deviation 0.8550	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Direct bilirubin, Day 42	-0.171 Micromoles (umol)/L Standard Deviation 2.2002	—	-0.855 Micromoles (umol)/L Standard Deviation 0.9873	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Total bilirubin, Day 7	-0.777 Micromoles (umol)/L Standard Deviation 6.4148	—	0.000 Micromoles (umol)/L Standard Deviation 3.6940	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Total bilirubin, Day 14	-0.933 Micromoles (umol)/L Standard Deviation 3.0935	—	0.428 Micromoles (umol)/L Standard Deviation 1.6372	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Total bilirubin, Day 28	-2.565 Micromoles (umol)/L Standard Deviation 4.1300	—	1.283 Micromoles (umol)/L Standard Deviation 3.7917	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Total bilirubin, Day 42	0.513 Micromoles (umol)/L Standard Deviation 5.9264	—	0.855 Micromoles (umol)/L Standard Deviation 2.9618	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Creatinine, Day 7	-6.4 Micromoles (umol)/L Standard Deviation 6.95	—	2.2 Micromoles (umol)/L Standard Deviation 11.12	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Creatinine, Day 14	-4.8 Micromoles (umol)/L Standard Deviation 9.97	—	-4.4 Micromoles (umol)/L Standard Deviation 11.41	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Creatinine, Day 28	-7.1 Micromoles (umol)/L Standard Deviation 6.97	—	0.0 Micromoles (umol)/L Standard Deviation 7.22	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Creatinine, Day 42	-8.8 Micromoles (umol)/L Standard Deviation 4.17	—	-2.2 Micromoles (umol)/L Standard Deviation 11.12	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Uric acid, Day 7	-10.3 Micromoles (umol)/L Standard Deviation 39.19	—	-7.4 Micromoles (umol)/L Standard Deviation 43.27	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Uric acid, Day 14	-17.8 Micromoles (umol)/L Standard Deviation 26.60	—	-14.9 Micromoles (umol)/L Standard Deviation 46.71	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Uric acid, Day 28	4.2 Micromoles (umol)/L Standard Deviation 56.99	—	-1.5 Micromoles (umol)/L Standard Deviation 38.05	—
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A Uric acid, Day 42	-26.2 Micromoles (umol)/L Standard Deviation 27.50	—	-7.4 Micromoles (umol)/L Standard Deviation 35.15	—