Trial Outcomes & Findings for Dose-Ranging Study in Treatment Naive Type 2 Diabetes Mellitus(T2DM) (NCT NCT00500331)

Results Overview

Fasted blood samples for HbA1c were collected at Baseline and Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Only those participants with a value at Baseline and at Week 12 (after Last Observation Carried Forward \[LOCF\]) were used for this analysis. Adjusted mean is presented as least square mean.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

334 participants

Primary outcome timeframe

Baseline (Week 0) and Week 12

Results posted on

2017-12-06

Participant Flow

This study was conducted at 121 centers of which 95 randomized participants, in 18 countries (9 European, 8 International, and the United States) from 23 January 2007 to 14 February 2008.

The Screening period was of 2 weeks. A glucose meter and detailed instructions for use were provided to all participants at the Screening visit for self- monitoring of fasting blood glucose levels and a Daily Glucose Monitoring Log for recording blood glucose information. Dietary and exercise advice was provided at randomization.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg Eligible participants received GSK189075 50 milligram (mg) tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Study STARTED	48	47	48	48	48	47	48
Overall Study COMPLETED	33	42	43	38	44	42	46
Overall Study NOT COMPLETED	15	5	5	10	4	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg Eligible participants received GSK189075 50 milligram (mg) tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Overall Study Adverse Event	0	2	0	1	2	2	0
Overall Study Lost to Follow-up	1	1	1	2	1	0	0
Overall Study Protocol Violation	3	1	1	0	1	1	1
Overall Study Withdrawal by Subject	4	0	1	5	0	1	1
Overall Study Lack of Efficacy	3	1	0	0	0	0	0
Overall Study Liver function test abnormality	0	0	1	0	0	0	0
Overall Study Increased serum creatinine from Baseline	0	0	0	0	0	1	0
Overall Study Didn't return for continuation of study	1	0	0	0	0	0	0
Overall Study Exclusion citeria not met on Visit 4	1	0	0	0	0	0	0
Overall Study Sponsor decided to withdraw participant	1	0	0	0	0	0	0
Overall Study Participant was randomized by mistake	1	0	0	0	0	0	0
Overall Study Diabetologist nurse in the study	0	0	1	0	0	0	0
Overall Study State ban of biological samples export	0	0	0	1	0	0	0
Overall Study Protocol violated	0	0	0	1	0	0	0

Baseline Characteristics

Dose-Ranging Study in Treatment Naive Type 2 Diabetes Mellitus(T2DM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=48 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=47 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=48 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=48 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=48 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=48 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.	Total n=334 Participants Total of all reporting groups
Sex: Female, Male Female	18 Participants n=5 Participants	23 Participants n=7 Participants	17 Participants n=5 Participants	19 Participants n=4 Participants	20 Participants n=21 Participants	20 Participants n=10 Participants	24 Participants n=115 Participants	141 Participants n=24 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	24 Participants n=7 Participants	31 Participants n=5 Participants	29 Participants n=4 Participants	28 Participants n=21 Participants	27 Participants n=10 Participants	24 Participants n=115 Participants	193 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants	4 Participants n=115 Participants	19 Participants n=24 Participants
Age, Continuous	55.9 Years STANDARD_DEVIATION 9.67 • n=5 Participants	54.3 Years STANDARD_DEVIATION 9.04 • n=7 Participants	56.0 Years STANDARD_DEVIATION 8.11 • n=5 Participants	55.7 Years STANDARD_DEVIATION 9.46 • n=4 Participants	54.6 Years STANDARD_DEVIATION 9.33 • n=21 Participants	52.4 Years STANDARD_DEVIATION 9.03 • n=10 Participants	54.5 Years STANDARD_DEVIATION 9.45 • n=115 Participants	54.8 Years STANDARD_DEVIATION 9.16 • n=24 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants	13 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	4 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants	37 Participants n=7 Participants	36 Participants n=5 Participants	41 Participants n=4 Participants	42 Participants n=21 Participants	40 Participants n=10 Participants	39 Participants n=115 Participants	276 Participants n=24 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	5 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	2 Participants n=10 Participants	2 Participants n=115 Participants	16 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Intent to Treat (ITT) Population with LOCF comprised of all randomized participants who received at least one dose of randomized study medication, had a Baseline assessment and had at least one corresponding on-therapy (scheduled or unscheduled) efficacy assessment. One extreme outlier participant had withdrawn from Placebo arm (lack of efficacy).

Fasted blood samples for HbA1c were collected at Baseline and Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Only those participants with a value at Baseline and at Week 12 (after Last Observation Carried Forward \[LOCF\]) were used for this analysis. Adjusted mean is presented as least square mean.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=45 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=43 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=44 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=45 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12	-0.31 Percentage of hemoglobin Standard Error 0.107	-1.04 Percentage of hemoglobin Standard Error 0.105	-0.96 Percentage of hemoglobin Standard Error 0.107	-1.05 Percentage of hemoglobin Standard Error 0.106	-1.21 Percentage of hemoglobin Standard Error 0.102	-1.38 Percentage of hemoglobin Standard Error 0.104	-1.07 Percentage of hemoglobin Standard Error 0.102

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 4 and Week 8

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis. One extreme outlier participant had withdrawn from Placebo arm due to lack of efficacy.

Fasted blood samples for HbA1c were collected at Baseline and Weeks 4 and 8. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=46 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=44 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=45 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline in HbA1c (%) at Weeks 4 and 8 Week 4	-0.30 Percentage of hemoglobin Standard Deviation 0.535	-0.77 Percentage of hemoglobin Standard Deviation 0.541	-0.69 Percentage of hemoglobin Standard Deviation 0.583	-0.64 Percentage of hemoglobin Standard Deviation 0.535	-0.83 Percentage of hemoglobin Standard Deviation 0.639	-0.84 Percentage of hemoglobin Standard Deviation 0.551	-0.39 Percentage of hemoglobin Standard Deviation 0.557
Change From Baseline in HbA1c (%) at Weeks 4 and 8 Week 8	-0.41 Percentage of hemoglobin Standard Deviation 0.689	-0.98 Percentage of hemoglobin Standard Deviation 0.712	-0.96 Percentage of hemoglobin Standard Deviation 0.827	-0.99 Percentage of hemoglobin Standard Deviation 0.751	-1.07 Percentage of hemoglobin Standard Deviation 0.747	-1.28 Percentage of hemoglobin Standard Deviation 0.636	-0.88 Percentage of hemoglobin Standard Deviation 0.713

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 4, Week 8 and Week 12

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis. One extreme outlier participant had withdrawn from Placebo arm due to lack of efficacy.

Fasted blood samples for FPG were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=46 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=44 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=43 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=46 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=46 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=46 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12 Week 4	-0.49 Millimoles per Liter (mmol/L) Standard Deviation 1.991	-0.56 Millimoles per Liter (mmol/L) Standard Deviation 1.512	-1.43 Millimoles per Liter (mmol/L) Standard Deviation 2.005	-1.49 Millimoles per Liter (mmol/L) Standard Deviation 2.314	-1.90 Millimoles per Liter (mmol/L) Standard Deviation 2.232	-2.48 Millimoles per Liter (mmol/L) Standard Deviation 2.491	-1.26 Millimoles per Liter (mmol/L) Standard Deviation 1.294
Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12 Week 8	-0.62 Millimoles per Liter (mmol/L) Standard Deviation 1.859	-0.91 Millimoles per Liter (mmol/L) Standard Deviation 2.073	-1.30 Millimoles per Liter (mmol/L) Standard Deviation 1.821	-1.76 Millimoles per Liter (mmol/L) Standard Deviation 2.137	-2.14 Millimoles per Liter (mmol/L) Standard Deviation 2.547	-2.78 Millimoles per Liter (mmol/L) Standard Deviation 2.531	-1.73 Millimoles per Liter (mmol/L) Standard Deviation 1.340
Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12 Week 12	-0.51 Millimoles per Liter (mmol/L) Standard Deviation 1.700	-0.89 Millimoles per Liter (mmol/L) Standard Deviation 1.960	-1.63 Millimoles per Liter (mmol/L) Standard Deviation 2.145	-1.80 Millimoles per Liter (mmol/L) Standard Deviation 2.107	-2.07 Millimoles per Liter (mmol/L) Standard Deviation 2.459	-2.76 Millimoles per Liter (mmol/L) Standard Deviation 2.821	-1.71 Millimoles per Liter (mmol/L) Standard Deviation 1.978

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT Population with LOCF. Only those participants with a value at Baseline up to Week 12 (after LOCF) were used for this analysis.

Fasted blood samples for fructosamine were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=39 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=37 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=37 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=36 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=41 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=39 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=43 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline to Week 12 in Fructosamine	5.7 Micromol per Liter (mcmol/L) Standard Deviation 51.24	-33.8 Micromol per Liter (mcmol/L) Standard Deviation 38.20	-35.7 Micromol per Liter (mcmol/L) Standard Deviation 41.69	-38.9 Micromol per Liter (mcmol/L) Standard Deviation 29.62	-41.9 Micromol per Liter (mcmol/L) Standard Deviation 35.54	-55.2 Micromol per Liter (mcmol/L) Standard Deviation 30.31	-34.7 Micromol per Liter (mcmol/L) Standard Deviation 38.84

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT Population with LOCF. Only those participants with a value at Baseline and up to Week 12 (after LOCF) were used for this analysis.

Fasted blood samples for insulin were collected up to Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=40 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=40 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=39 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=41 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=43 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=42 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline to Week 12 in Fasting Insulin	-30.6 Picomol per Liter (pmol/L) Standard Deviation 171.35	0.3 Picomol per Liter (pmol/L) Standard Deviation 58.69	-20.7 Picomol per Liter (pmol/L) Standard Deviation 60.75	-9.7 Picomol per Liter (pmol/L) Standard Deviation 43.95	-25.8 Picomol per Liter (pmol/L) Standard Deviation 60.94	-15.1 Picomol per Liter (pmol/L) Standard Deviation 57.59	-2.1 Picomol per Liter (pmol/L) Standard Deviation 49.60

SECONDARY outcome

Timeframe: Week 12

Population: ITT Population with Last Observation Carried Forward (LOCF). Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.

Fasted blood samples for HbA1c were collected at Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Number of participants at Week 12 with: HbA1c \<= 6.5%, HbA1c \<7.0%; FPG \<7 mmo/L (126 milligram/deciliter \[mg/dL\]), FPG \<7.8 mmol/L (140 mg/dL); FPG \<5.5 mmol/L (100 mg/dL); a decrease from Baseline of HbA1c \>= 0.7%; a decrease from Baseline of FPG ≥1.7 mmol/L (30 mg/dL) are presented.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=46 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=44 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=45 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L HbA1c <7.0%	9 Participants	20 Participants	18 Participants	22 Participants	28 Participants	29 Participants	21 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L FPG <7 mmo/L	4 Participants	16 Participants	20 Participants	18 Participants	22 Participants	22 Participants	21 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L FPG <7.8 mmol/L	13 Participants	24 Participants	26 Participants	27 Participants	33 Participants	34 Participants	31 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L Decrease from Baseline of FPG ≥1.7 mmol/L	8 Participants	15 Participants	19 Participants	21 Participants	24 Participants	30 Participants	23 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L FPG <5.5 mmol/L	0 Participants	4 Participants	2 Participants	5 Participants	4 Participants	3 Participants	2 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L Decrease from Baseline of HbA1c >= 0.7%	16 Participants	33 Participants	27 Participants	33 Participants	36 Participants	39 Participants	28 Participants
Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L HbA1c <= 6.5%	3 Participants	10 Participants	8 Participants	11 Participants	17 Participants	17 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 4, Week 8 and Week 12

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at specified visits (after LOCF) were used for this analysis.

Fasted samples for TC, LDL-C, HDL-C and TG were collected at Week 12. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent Change based on log-transformed data: 100\*(exponentiated(mean change on log scale)-1)

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=46 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=44 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=45 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) HDL-C: Week 8	0.00 Percent change Interval -31.6 to 19.1	6.20 Percent change Interval -20.6 to 40.6	5.00 Percent change Interval -20.7 to 58.3	3.09 Percent change Interval -41.4 to 93.5	7.14 Percent change Interval -15.8 to 59.2	0.00 Percent change Interval -42.7 to 52.2	8.20 Percent change Interval -13.2 to 48.1
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) LDL-C: Week 8	3.17 Percent change Interval -63.0 to 56.4	8.67 Percent change Interval -38.7 to 53.1	3.62 Percent change Interval -32.6 to 125.0	8.96 Percent change Interval -37.9 to 118.8	7.57 Percent change Interval -24.8 to 67.2	4.44 Percent change Interval -39.5 to 119.5	-2.24 Percent change Interval -47.8 to 55.2
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) LDL-C: Week 12	3.17 Percent change Interval -60.4 to 56.4	6.69 Percent change Interval -39.4 to 90.2	3.57 Percent change Interval -29.7 to 355.0	3.93 Percent change Interval -23.0 to 102.9	11.43 Percent change Interval -36.7 to 92.0	14.89 Percent change Interval -23.7 to 125.6	1.18 Percent change Interval -61.9 to 51.8
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) HDL-C: Week 4	-1.97 Percent change Interval -23.5 to 23.5	5.43 Percent change Interval -11.5 to 45.8	3.69 Percent change Interval -31.3 to 54.2	5.13 Percent change Interval -29.3 to 93.3	5.69 Percent change Interval -17.0 to 56.2	0.00 Percent change Interval -33.0 to 32.9	9.18 Percent change Interval -17.6 to 57.5
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) HDL-C: Week 12	0.00 Percent change Interval -31.6 to 32.6	5.56 Percent change Interval -28.6 to 42.2	4.96 Percent change Interval -16.7 to 70.8	6.70 Percent change Interval -14.4 to 90.3	11.93 Percent change Interval -15.8 to 51.7	4.27 Percent change Interval -50.2 to 36.4	10.00 Percent change Interval -12.6 to 46.2
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TG: Week 4	-8.35 Percent change Interval -44.3 to 110.1	-3.45 Percent change Interval -48.1 to 177.8	6.32 Percent change Interval -55.1 to 112.1	-13.42 Percent change Interval -56.8 to 133.6	-13.04 Percent change Interval -74.8 to 207.1	-4.62 Percent change Interval -48.2 to 256.3	-7.22 Percent change Interval -68.6 to 76.9
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TG: Week 8	-1.66 Percent change Interval -67.2 to 135.2	-9.09 Percent change Interval -61.3 to 88.8	0.59 Percent change Interval -47.4 to 122.5	-10.01 Percent change Interval -57.9 to 100.0	-13.35 Percent change Interval -51.9 to 207.1	-7.30 Percent change Interval -60.9 to 121.6	-0.79 Percent change Interval -71.1 to 82.5
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TG: Week 12	3.32 Percent change Interval -58.6 to 135.2	-10.91 Percent change Interval -60.2 to 213.0	10.92 Percent change Interval -45.3 to 232.5	-4.71 Percent change Interval -56.8 to 73.6	-15.28 Percent change Interval -66.8 to 255.7	-9.97 Percent change Interval -58.4 to 123.4	-7.19 Percent change Interval -58.2 to 116.7
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TC: Week 4	0.47 Percent change Interval -57.4 to 25.8	1.85 Percent change Interval -22.9 to 65.0	1.62 Percent change Interval -17.6 to 34.8	4.13 Percent change Interval -40.1 to 63.9	4.43 Percent change Interval -37.9 to 36.6	2.39 Percent change Interval -22.7 to 54.4	2.29 Percent change Interval -42.0 to 29.5
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TC: Week 8	0.82 Percent change Interval -48.4 to 48.4	3.49 Percent change Interval -31.3 to 43.1	3.64 Percent change Interval -31.5 to 30.0	4.49 Percent change Interval -14.0 to 73.7	5.31 Percent change Interval -19.9 to 41.2	0.00 Percent change Interval -24.3 to 49.9	1.06 Percent change Interval -40.2 to 34.9
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) TC: Week 12	4.75 Percent change Interval -46.5 to 76.6	3.39 Percent change Interval -28.1 to 43.4	5.45 Percent change Interval -19.0 to 84.6	3.97 Percent change Interval -16.8 to 67.1	9.82 Percent change Interval -16.3 to 43.3	2.77 Percent change Interval -17.5 to 52.5	-2.05 Percent change Interval -48.3 to 31.4
Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C]) LDL-C: Week 4	0.82 Percent change Interval -75.6 to 68.5	0.83 Percent change Interval -27.3 to 117.0	0.37 Percent change Interval -30.9 to 75.0	6.91 Percent change Interval -52.9 to 84.1	10.03 Percent change Interval -39.0 to 59.6	7.02 Percent change Interval -37.0 to 130.3	0.00 Percent change Interval -54.0 to 50.0

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT population with LOCF for withdrawn participants or missing values.

Weight of participants was measured from Baseline (Week 0) to Week 12 and recorded in the case report form (CRF). Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=46 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=44 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=45 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline to Week 12 in Body Weight	-0.49 Kilograms Standard Deviation 1.719	-1.78 Kilograms Standard Deviation 3.197	-2.41 Kilograms Standard Deviation 2.850	-2.38 Kilograms Standard Deviation 2.875	-3.52 Kilograms Standard Deviation 2.874	-4.00 Kilograms Standard Deviation 2.945	0.96 Kilograms Standard Deviation 2.425

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT population with LOCF for withdrawn participants or missing values.

Waist circumference of participants was measured from Baseline (Week 0) to Week 12 and recorded in the CRF. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=41 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=43 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=43 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=43 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=42 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=44 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline to Week 12 in Waist Circumference	-0.7 Centimeters Standard Deviation 2.92	-1.2 Centimeters Standard Deviation 3.58	-2.0 Centimeters Standard Deviation 4.51	-2.2 Centimeters Standard Deviation 3.43	-2.6 Centimeters Standard Deviation 3.31	-2.4 Centimeters Standard Deviation 4.26	1.3 Centimeters Standard Deviation 4.82

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12 (24-hour urine collection)

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

A 24-hour urine collection was obtained from all participants at Baseline (Week 0) and Week 12 to measure glucose. Participants were provided with urine collection bottles and cooler prior to these visits and instructed that the urine collections must be kept cold and dropped off at the clinic prior to or at the scheduled visits. Site staff queried participants to determine whether the sample represented a full 24-hour collection. The total volume and the sample date and time were recorded. The entire 24-hour urine collection was well mixed in one container and a urine aliquot obtained. Samples were assayed for glucose. The 24-hour collections were used to derive 24-hour urine glucose excretion corrected for filtered load. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=23 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=28 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=27 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=27 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=25 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=27 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=37 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline in 24-hour Percent of Filtered Glucose Excreted in Urine	-1.09 Percentage of filtered glucose molecules Standard Deviation 5.731	27.96 Percentage of filtered glucose molecules Standard Deviation 15.693	40.43 Percentage of filtered glucose molecules Standard Deviation 16.144	38.98 Percentage of filtered glucose molecules Standard Deviation 19.006	42.41 Percentage of filtered glucose molecules Standard Deviation 22.708	52.39 Percentage of filtered glucose molecules Standard Deviation 15.264	-0.99 Percentage of filtered glucose molecules Standard Deviation 2.313

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)

Population: The OGTT Population with LOCF which comprised of participants in the ITT population having evaluable Baseline and corresponding on-therapy OGTT measurements (for at least one of the measured parameters of FPG, C-Peptide or Insulin). Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.

Post-prandial assessments of glucose were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time "0" started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=9 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=8 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=12 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=8 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=10 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=14 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=7 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline in Plasma Glucose Area Under the Curve (AUC) During a 2-hour Oral Glucose Tolerance Test (OGTT)	-0.90 Millimolhour per Liter (mmolhr/L) Standard Deviation 5.739	-6.31 Millimolhour per Liter (mmolhr/L) Standard Deviation 5.907	-6.71 Millimolhour per Liter (mmolhr/L) Standard Deviation 7.326	-7.69 Millimolhour per Liter (mmolhr/L) Standard Deviation 3.791	-6.06 Millimolhour per Liter (mmolhr/L) Standard Deviation 2.837	-7.59 Millimolhour per Liter (mmolhr/L) Standard Deviation 3.065	-6.55 Millimolhour per Liter (mmolhr/L) Standard Deviation 3.841

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12 (0 to 2-hour OGTT)

Population: OGTT with LOCF Population. Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.

Post-prandial assessments of insulin were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time "0" started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=8 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=12 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=8 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=9 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=13 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=9 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline in Insulin AUC During a 2-hour OGTT	-5.3 Picomolhour per Liter (pmolhr/L) Standard Deviation 177.23	162.4 Picomolhour per Liter (pmolhr/L) Standard Deviation 362.82	-70.9 Picomolhour per Liter (pmolhr/L) Standard Deviation 193.77	66.6 Picomolhour per Liter (pmolhr/L) Standard Deviation 213.07	-173.9 Picomolhour per Liter (pmolhr/L) Standard Deviation 143.52	-97.8 Picomolhour per Liter (pmolhr/L) Standard Deviation 224.24	10.0 Picomolhour per Liter (pmolhr/L) Standard Deviation 128.77

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12 (0 to 2 hour OGTT)

Population: OGTT with LOCF Population. Only those participants with a value at Baseline and at Week 12 (after LOCF) were used for this analysis.

Post-prandial assessments of C-peptide were performed at Baseline (Week 0) and at Week 12 using a 2-hour OGTT in a subgroup of participants at selected sites who agreed to participate. Participants were required to fast for at least 8 hours prior to the test. Seventy-five (75) g of standard oral glucose solution was administered 15 minutes after the morning administration of study medication (Week 12) and in the place of breakfast at Week 0 (i.e., at Week 0 the OGTT was completed prior to administration of study medication). Time "0" started when the participants drank the glucose solution. Blood samples were collected at the following times relative to the administration of oral glucose: -30 min (pre-glucose), -20 min (pre-glucose), 20 min, 30 min, 1 hour, 1.5 hour and 2 hour post glucose administration. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=8 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=12 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=7 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=9 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=12 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=9 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Change From Baseline in C-peptide AUC During a 2-hr OGTT	-0.140 Nanomolhour per Liter (nmolhr/L) Standard Deviation 0.7348	0.654 Nanomolhour per Liter (nmolhr/L) Standard Deviation 1.4023	-0.156 Nanomolhour per Liter (nmolhr/L) Standard Deviation 1.0566	-0.026 Nanomolhour per Liter (nmolhr/L) Standard Deviation 0.9606	-0.476 Nanomolhour per Liter (nmolhr/L) Standard Deviation 0.4668	-0.175 Nanomolhour per Liter (nmolhr/L) Standard Deviation 0.8322	-0.239 Nanomolhour per Liter (nmolhr/L) Standard Deviation 0.6732

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: Safety population which comprised of all participants who received at least one dose of study medication.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is 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 or is medically significant.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=47 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=48 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=48 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=48 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=48 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Number of Participants With On-therapy Adverse Events (AE) and Serious Adverse Events (SAE) AE	18 Participants	18 Participants	17 Participants	19 Participants	18 Participants	22 Participants	22 Participants
Number of Participants With On-therapy Adverse Events (AE) and Serious Adverse Events (SAE) SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 14 weeks

Population: Safety Population.

Hypoglycemia is low blood glucose or low blood sugar. Hypoglycemic events were collected separately and reported separately from AE, including supplemental data which were not collected for AE. However, any hypoglycemic event which met the criteria for a SAE was included in the SAE summaries. The number of participants in each group that experienced a hypoglycemic event was summarized by frequency of the events.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=47 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=48 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=48 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=48 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=48 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Number of Participants With On-therapy Hypoglycemia	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 14 weeks

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

Vital signs included heart rate and blood pressure. Heart rate and blood pressure were taken before blood draws were performed. Participants were asked to refrain from smoking for at least 30 minutes prior to vital sign measurements. Heart rate and blood pressure was measured pre-dose in duplicate at the specified visits, after the participant had been lying quietly for 5 minutes, and then in duplicate 3 minutes after standing up. Heart rate was measured at the same time as blood pressure using the standardized blood pressure equipment that was provided. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=47 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=48 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=48 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=48 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=47 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=48 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern Low SBP	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern High SBP	3 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern High DBP	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern Low DBP	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern High heart rate	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern Low heart rate	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Early withdrawal (Between Week 12 and Week 14)

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

Full 12-lead ECGs were recorded at screening, Baseline (Week 0), Week 4, Week 12 or early withdrawal, and Week 14 (Follow-up) using an ECG machine that automatically calculated the heart rate and measured the PR, QRS, QT and corrected QT (QTc) intervals. All 12-lead ECGs were read locally by the Investigator or his/her designate and were forwarded electronically to the central reader for interpretation. If the QTc was \>500 milliseconds (msec) on the locally read ECG recording, an additional 2 ECG recordings at 10 minute intervals were made at that visit. If the average QTc for the 3 recordings was \>500 msec, the participant was withdrawn from the study.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Eligible participants received matching placebo, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 50 mg n=45 Participants Eligible participants received GSK189075 50 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 100 mg n=43 Participants Eligible participants received GSK189075 100 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 250 mg n=44 Participants Eligible participants received GSK189075 250 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 500 mg n=47 Participants Eligible participants received GSK189075 500 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	GSK189075 1000 mg n=46 Participants Eligible participants received GSK189075 1000 mg tablets, orally, twice daily before breakfast and dinner for 12 weeks.	Pioglitazone 30 mg n=47 Participants Eligible participants received Pioglitazone 30 mg tablets, orally, once daily before breakfast for 12 weeks.
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern PR interval > 300 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern QRS Duration > 200 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern QTc(Bazett) > 500 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern QTc(Fridericia) > 500 msec	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 14 weeks

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

Participants were instructed to fast for at least 8 hours prior to all study visits for the collection of laboratory samples. An additional fasting blood sample (serum and plasma) was drawn at Week 0, Week 4, Week 6 and Week 12 or at early withdrawal (up to 14 weeks) and kept in long-term storage for future testing of biomarkers for diabetes and complications of the disease. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.