Trial Outcomes & Findings for Efficacy and Safety of Albiglutide in Treatment of Type 2 Diabetes (NCT NCT00838903)

Last Updated: 2017-01-09

Results Overview

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c value is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 104 minus the value at BL. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region. Difference of least squares means (albiglutide - placebo, albiglutide - sitagliptin, albiglutide - glimepiride) is from the ANCOVA model. The last observation carried forward (LOCF) method was used to impute missing post-Baseline HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1049 participants

Primary outcome timeframe

Baseline and Week 104

Results posted on

2017-01-09

Participant Flow

Eligible participants (par.) entered a 2-week Screening Period, a 4-week Run-in/Stabilization Period, a 156-week Treatment Period, and a 8-week post-treatment Follow-up Period. A total of 1525 par. were screened, 1049 were randomized and 1012 par. received at least 1 dose of study treatment.

Participant milestones

Participant milestones
Measure	Placebo Plus Metformin Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Treatment Period (156 Weeks) STARTED	101	302	307	302
Treatment Period (156 Weeks) Missing Active Treatment Status	1	0	0	0
Treatment Period (156 Weeks) COMPLETED	55	190	191	192
Treatment Period (156 Weeks) NOT COMPLETED	46	112	116	110
Follow-up Period (8 Weeks) STARTED	101	302	307	302
Follow-up Period (8 Weeks) COMPLETED	75	237	243	244
Follow-up Period (8 Weeks) NOT COMPLETED	26	65	64	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Plus Metformin Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Treatment Period (156 Weeks) Adverse Event	5	13	17	25
Treatment Period (156 Weeks) Protocol Violation	1	6	6	5
Treatment Period (156 Weeks) Noncompliance	9	13	12	6
Treatment Period (156 Weeks) Severe or Repeated Hypoglycaemia	0	0	1	0
Treatment Period (156 Weeks) Lost to Follow-up	4	16	15	13
Treatment Period (156 Weeks) Withdrawal by Subject	20	55	56	53
Treatment Period (156 Weeks) Physician Decision	1	2	1	2
Treatment Period (156 Weeks) Termination of Study/Site by GSK	3	5	5	4
Treatment Period (156 Weeks) Patient and PI Decision to Discontinue	0	1	0	0
Treatment Period (156 Weeks) Poor Glycemic Control	0	0	0	1
Treatment Period (156 Weeks) Poor Therapeutic Response	1	0	0	0
Treatment Period (156 Weeks) Pregnancy	0	0	1	0
Treatment Period (156 Weeks) PI Decided for Safety Purpose	0	0	1	0
Treatment Period (156 Weeks) Site closed	0	0	1	0
Treatment Period (156 Weeks) Site Closed and Subject Withdrew Consent	1	0	0	0
Treatment Period (156 Weeks) Subject Migrated to Other Country	0	1	0	1
Treatment Period (156 Weeks) Missing Active Treatment Status	1	0	0	0
Follow-up Period (8 Weeks) Adverse Event	0	0	3	1
Follow-up Period (8 Weeks) Noncompliance	2	8	5	5
Follow-up Period (8 Weeks) Lost to Follow-up	6	28	22	24
Follow-up Period (8 Weeks) Did Not Enter Follow-up Period	5	7	12	7
Follow-up Period (8 Weeks) Subject Withdrawn from Follow-up	8	13	14	14
Follow-up Period (8 Weeks) Physician Decision	1	1	1	1
Follow-up Period (8 Weeks) Termination of Study/Site by GSK	3	4	6	4
Follow-up Period (8 Weeks) ICF Withdrawn	0	1	0	0
Follow-up Period (8 Weeks) Investigator Stopped Study at Site	0	1	0	0
Follow-up Period (8 Weeks) Subject Moved out of Town	0	0	0	1
Follow-up Period (8 Weeks) Missing	1	2	1	1

Baseline Characteristics

Efficacy and Safety of Albiglutide in Treatment of Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Plus Metformin n=101 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=302 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=307 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=302 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Total n=1012 Participants Total of all reporting groups
Age, Continuous	56.1 Years STANDARD_DEVIATION 10.01 • n=5 Participants	54.3 Years STANDARD_DEVIATION 9.81 • n=7 Participants	54.4 Years STANDARD_DEVIATION 9.97 • n=5 Participants	54.3 Years STANDARD_DEVIATION 10.12 • n=4 Participants	54.5 Years STANDARD_DEVIATION 9.97 • n=21 Participants
Gender Female	51 Participants n=5 Participants	163 Participants n=7 Participants	149 Participants n=5 Participants	167 Participants n=4 Participants	530 Participants n=21 Participants
Gender Male	50 Participants n=5 Participants	139 Participants n=7 Participants	158 Participants n=5 Participants	135 Participants n=4 Participants	482 Participants n=21 Participants
Race/Ethnicity, Customized African American/African Heritage	23 Participants n=5 Participants	35 Participants n=7 Participants	39 Participants n=5 Participants	53 Participants n=4 Participants	150 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	9 Participants n=5 Participants	22 Participants n=7 Participants	25 Participants n=5 Participants	17 Participants n=4 Participants	73 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	10 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	3 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	11 Participants n=4 Participants	34 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	64 Participants n=5 Participants	225 Participants n=7 Participants	220 Participants n=5 Participants	214 Participants n=4 Participants	723 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline and Week 104

Population: Intent-to-Treat (ITT) Population with LOCF: all randomized par. who received \>=1 dose of study medication and who had a BL assessment and \>=1 post-BL assessment of HbA1c. Only par. with a value at BL and at the specified visit were analyzed. Values were carried forward for par. who were rescued or discontinued from active treatment before Week 104.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=97 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=297 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=299 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=293 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 104	0.27 Percentage of HbA1c in the blood Standard Error 0.113	-0.28 Percentage of HbA1c in the blood Standard Error 0.065	-0.36 Percentage of HbA1c in the blood Standard Error 0.064	-0.63 Percentage of HbA1c in the blood Standard Error 0.065

SECONDARY outcome

Timeframe: Baseline and Week 156

Population: Intent-to-Treat (ITT) Population with observed values. Only those par. with a value at Baseline and at the specified visit were analyzed.

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed .

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=16 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=88 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=102 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=115 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline in HbA1c at Week 156	-0.46 Percentage of HbA1c in the blood Standard Deviation 0.820	-0.56 Percentage of HbA1c in the blood Standard Deviation 1.160	-0.59 Percentage of HbA1c in the blood Standard Deviation 0.999	-0.88 Percentage of HbA1c in the blood Standard Deviation 0.959

SECONDARY outcome

Timeframe: Baseline and Week 104

Population: Intent-to-Treat (ITT) Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 104.

The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline FPG + Baseline HbA1c category + prior myocardial infarction history + age category + region.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=100 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=299 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=302 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=296 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 104	0.55 Millimoles per liter (mmol/L) Standard Error 0.277	-0.12 Millimoles per liter (mmol/L) Standard Error 0.160	-0.41 Millimoles per liter (mmol/L) Standard Error 0.159	-0.98 Millimoles per liter (mmol/L) Standard Error 0.161

SECONDARY outcome

Timeframe: Baseline and Week 156

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed.

The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=16 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=88 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=98 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=112 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline in FPG at Week 156	-0.11 Millimoles per liter (mmol/L) Standard Deviation 1.498	-0.50 Millimoles per liter (mmol/L) Standard Deviation 2.519	-0.71 Millimoles per liter (mmol/L) Standard Deviation 2.684	-1.30 Millimoles per liter (mmol/L) Standard Deviation 2.602

SECONDARY outcome

Timeframe: Week 104

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 104.

The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 52) were assessed.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=97 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=297 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=299 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=293 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 104 HbA1c <6.5%	7 Participants	45 Participants	40 Participants	50 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 104 HbA1c <7.0%	15 Participants	94 Participants	94 Participants	113 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 104 HbA1c <7.5%	27 Participants	132 Participants	147 Participants	172 Participants

SECONDARY outcome

Timeframe: Week 156

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed.

The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 156) were assessed.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=16 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=88 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=102 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=115 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 HbA1c <6.5%	4 Participants	23 Participants	15 Participants	31 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 HbA1c <7.0%	7 Participants	44 Participants	44 Participants	69 Participants
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 HbA1c <7.5%	13 Participants	69 Participants	69 Participants	90 Participants

SECONDARY outcome

Timeframe: From the start of study medication until the end of the treatment (up to Week 156)

Population: ITT Population. Only those participants with a value at Baseline and at the specified visit were analyzed.

Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue.The conditions for hyperglycemic rescue were as follows: FPG \>=280 milligrams/deciliter (mg/dL) between \>=Week 2 and \<Week 4; FPG \>=250 mg/dL between \>=Week 4 and \<Week 12; HbA1c \>=8.5% and a \<=0.5% reduction from Baseline between \>=Week 12 and \<Week 24; HbA1c \>=8.5% between \>=Week 24 and \<Week 48; HbA1c \>=8.0% between \>= Week 48 and \<Week 156. Participants could have been rescued at any time on or after Week 2. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus 1 day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus 1 day for participants not requiring rescue. This time was divided by 7 to express the result in week

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=100 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=300 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=302 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=297 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Time to Hyperglycemia Rescue	67.71 Weeks Interval 53.14 to 122.14	NA Weeks There were few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.	NA Weeks There were few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.	NA Weeks There were few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.

SECONDARY outcome

Timeframe: Baseline and Week 104

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=100 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=300 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=302 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=296 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline in Body Weight at Week 104	-1.00 Kilograms Standard Error 0.411	-0.86 Kilograms Standard Error 0.237	1.17 Kilograms Standard Error 0.237	-1.21 Kilograms Standard Error 0.239

SECONDARY outcome

Timeframe: Baseline and Week 156

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

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Placebo Plus Metformin n=16 Participants Participants received metformin \>=1500 milligrams (mg) daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Sitagliptin 100 mg Plus Metformin n=89 Participants Participants received sitagliptin 100 mg daily plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Glimepiride 2 mg Plus Metformin n=102 Participants Participants received glimepiride 2 mg daily (with masked up-titration to 4 mg daily if required) plus metformin \>=1500 mg daily plus matching albiglutide placebo as a subcutaneous injection weekly via a fully disposable pen injector system plus matching sitagliptin placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.	Albiglutide 30 mg Plus Metformin n=116 Participants Participants received albiglutide 30 mg weekly (with masked up-titration to 50 mg weekly if required) as a subcutaneous injection via a fully disposable pen injector system plus metformin \>=1500 mg daily plus matching sitagliptin placebo plus matching glimepiride placebo from Week 1 to Week 156. All participants returned for the 8-week post-treatment Follow-up Period.
Change From Baseline in Body Weight at Week 156	-3.61 Kilograms Standard Deviation 3.460	-2.05 Kilograms Standard Deviation 4.109	0.98 Kilograms Standard Deviation 4.760	-2.31 Kilograms Standard Deviation 5.093

Adverse Events

Placebo Plus Metformin

Serious events: 15 serious events

Other events: 75 other events

Deaths: 0 deaths

Sitagliptin 100 mg Plus Metformin

Serious events: 32 serious events

Other events: 229 other events

Deaths: 0 deaths

Glimepiride 2 mg Plus Metformin

Serious events: 36 serious events

Other events: 258 other events

Deaths: 0 deaths

Albiglutide 30 mg Plus Metformin

Serious events: 44 serious events

Other events: 242 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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.
Publication restrictions are in place

Restriction type: OTHER