Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes
Brief summary
The purpose of this study is to determine the safety and efficacy of albiglutide in subjects with type 2 diabetes
Interventions
DRUGplacebo to match albiglutide
albiglutide matching placebo weekly subcutaneous injection
BIOLOGICALalbiglutide
albiglutide weekly subcutaneous injection
DRUGmetformin
metformin
DRUGglimepiride
glimepiride
DRUGpioglitazone
pioglitazone
DRUGplacebo to match pioglitazone
pioglitazone matching placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* type 2 diabetes * BMI 20-45kg/m2 inclusive
Exclusion criteria
* females who are pregnant, lactating, or less than 6 weeks post-partum * current symptomatic heart failure (NYHA Class II-IV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 | Baseline and Week 52 | 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 52 minus the value at BL. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region. The last observation carried forward (LOCF) method was used to impute missing post-BL 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. Nine par. with post-BL values obtained \>14 days after the last dose or after hyperglycemic rescue were included in the analysis population but were not analyzed for this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | Baseline and Week 52 | 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. |
| Change From Baseline in FPG at Week 104 and Week 156 | Baseline, Week 104, and Week 156 | 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. |
| Time to Hyperglycemia Rescue | From the start of study medication until the end of the treatment (up to Week 156) | Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia 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 weeks. |
| Change From Baseline in HbA1c at Week 104 and Week 156 | Baseline, Week 104, and Week 156 | 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 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. |
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | Week 156 | The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 156) was assessed. |
| Change From Baseline in Body Weight at Week 52 | Baseline and Week 52 | 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 pre-rescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region. |
| Change From Baseline in Body Weight at Week 104 and Week 156 | Baseline, Week 104, and Week 156 | 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. |
| Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | Week 52 | The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 52) was assessed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52. |
Countries
Germany, Hong Kong, India, Peru, Philippines, Russia, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Participants (par.) who met eligibility criteria and completed a 6- to 8-week Run-in/Stabilization Period were then randomized to a 156-week Treatment Period, followed by 8 weeks of post-treatment follow-up. A total of 992 par. were screened; 685 par. were randomized, and 663 par. received \>=1 treatment dose.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Metformin + Glimepiride Participants received albiglutide matching placebo as a subcutaneous injection weekly via a fully disposable pen injector system with open-label glimepiride (4 milligrams \[mg\] daily orally) with metformin (\>=1500 mg daily orally). Participants did not receive investigational product during the Follow-up Period. | 115 |
| Pioglitazone + Metformin + Glimepiride Participants received pioglitazone (30 mg daily orally; with treatment-masked uptitration if needed to 45 mg) and albiglutide-matching placebo weekly as a subcutaneous injection via a fully disposable pen injector system with open-label glimepiride (4 mg daily orally) with metformin (\>=1500 mg daily orally). Participants did not receive investigational product during the Follow-up Period. | 277 |
| Albiglutide + Metformin + Glimepiride Participants received pioglitazone-matching placebo daily orally and albiglutide (30 mg weekly; treatment-masked uptitration if needed to 50 mg weekly) as a subcutaneous injection via a fully disposable pen injector system with open-label glimepiride (4 mg daily orally) with metformin (\>=1500 mg daily orally). Participants did not receive investigational product during the Follow-up Period. | 271 |
| Total | 663 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow-up Period (FUP) (8 Weeks) | Adverse Event | 1 | 2 | 1 |
| Follow-up Period (FUP) (8 Weeks) | Informed Consent Recalled by Participant | 1 | 0 | 0 |
| Follow-up Period (FUP) (8 Weeks) | Investigator Closed Study at Site | 1 | 0 | 0 |
| Follow-up Period (FUP) (8 Weeks) | Lost to Follow-up | 8 | 20 | 29 |
| Follow-up Period (FUP) (8 Weeks) | Missing Follow-up Status | 0 | 1 | 1 |
| Follow-up Period (FUP) (8 Weeks) | Noncompliance | 1 | 0 | 5 |
| Follow-up Period (FUP) (8 Weeks) | Physician Decision | 0 | 0 | 1 |
| Follow-up Period (FUP) (8 Weeks) | Site Closed | 0 | 1 | 0 |
| Follow-up Period (FUP) (8 Weeks) | Site Closing and Withdrew Consent | 1 | 0 | 1 |
| Follow-up Period (FUP) (8 Weeks) | Termination of Study by Sponsor | 3 | 10 | 5 |
| Follow-up Period (FUP) (8 Weeks) | Unable to Complete Follow-up | 0 | 1 | 0 |
| Follow-up Period (FUP) (8 Weeks) | Withdrawal by Subject | 12 | 21 | 19 |
| Treatment Period (TP) (156 Weeks) | Adverse Event | 11 | 29 | 22 |
| Treatment Period (TP) (156 Weeks) | Lost to Follow-up | 3 | 12 | 7 |
| Treatment Period (TP) (156 Weeks) | Missing | 0 | 1 | 0 |
| Treatment Period (TP) (156 Weeks) | Noncompliance | 5 | 6 | 16 |
| Treatment Period (TP) (156 Weeks) | Persistant Elevated HbA1c Results | 0 | 0 | 1 |
| Treatment Period (TP) (156 Weeks) | Physician Decision | 1 | 6 | 1 |
| Treatment Period (TP) (156 Weeks) | Pregnancy | 0 | 1 | 1 |
| Treatment Period (TP) (156 Weeks) | Protocol Violation | 4 | 7 | 1 |
| Treatment Period (TP) (156 Weeks) | Site Closed | 1 | 2 | 0 |
| Treatment Period (TP) (156 Weeks) | Sponsor Decision on Blinding | 0 | 0 | 1 |
| Treatment Period (TP) (156 Weeks) | Termination of Site by Sponsor | 3 | 8 | 5 |
| Treatment Period (TP) (156 Weeks) | Withdrawal by Subject | 32 | 46 | 64 |
Baseline characteristics
| Characteristic | Pioglitazone + Metformin + Glimepiride | Albiglutide + Metformin + Glimepiride | Placebo + Metformin + Glimepiride | Total |
|---|---|---|---|---|
| Age, Continuous | 55.7 Years STANDARD_DEVIATION 9.39 | 54.5 Years STANDARD_DEVIATION 9.47 | 55.7 Years STANDARD_DEVIATION 9.59 | 55.2 Years STANDARD_DEVIATION 9.46 |
| Gender Female | 129 Participants | 136 Participants | 45 Participants | 310 Participants |
| Gender Male | 148 Participants | 135 Participants | 70 Participants | 353 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 24 Participants | 34 Participants | 10 Participants | 68 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 10 Participants | 22 Participants | 9 Participants | 41 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 6 Participants | 8 Participants | 6 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 8 Participants | 12 Participants | 2 Participants | 22 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 24 Participants | 14 Participants | 7 Participants | 45 Participants |
| Race/Ethnicity, Customized Mexican American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 201 Participants | 176 Participants | 79 Participants | 456 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 81 / 115 | 228 / 277 | 228 / 271 |
| serious Total, serious adverse events | 21 / 115 | 48 / 277 | 39 / 271 |
Outcome results
Primary
Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52
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 52 minus the value at BL. Based on analysis of covariance (ANCOVA): change = treatment + BL HbA1c + prior myocardial infarction history + age category + region. The last observation carried forward (LOCF) method was used to impute missing post-BL 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. Nine par. with post-BL values obtained \>14 days after the last dose or after hyperglycemic rescue were included in the analysis population but were not analyzed for this endpoint.
Time frame: Baseline and Week 52
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 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 | 0.33 Percentage of HbA1c in the blood | Standard Error 0.083 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 | -0.80 Percentage of HbA1c in the blood | Standard Error 0.055 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 | -0.55 Percentage of HbA1c in the blood | Standard Error 0.055 |
p-value: <0.000195% CI: [-1.07, -0.68]ANCOVA
p-value: 0.268595% CI: [0.1, 0.4]t-test, 1 sided
Secondary
Change From Baseline in Body Weight at Week 104 and Week 156
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.
Time frame: Baseline, Week 104, and Week 156
Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 104, n=12, 130, 104 | -2.16 Kilograms | Standard Deviation 3.603 |
| Placebo + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 156, n=9, 90, 71 | -4.47 Kilograms | Standard Deviation 5.38 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 104, n=12, 130, 104 | 6.28 Kilograms | Standard Deviation 6.189 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 156, n=9, 90, 71 | 6.52 Kilograms | Standard Deviation 6.332 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 104, n=12, 130, 104 | -0.90 Kilograms | Standard Deviation 3.721 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 104 and Week 156 | Week 156, n=9, 90, 71 | -1.53 Kilograms | Standard Deviation 3.88 |
Secondary
Change From Baseline in Body Weight at Week 52
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 pre-rescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region.
Time frame: Baseline and Week 52
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 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 52 | -0.40 Kilograms | Standard Error 0.362 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 52 | 4.43 Kilograms | Standard Error 0.235 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in Body Weight at Week 52 | -0.42 Kilograms | Standard Error 0.237 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
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.
Time frame: Baseline and Week 52
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 52.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | 0.64 Millimoles per liter (mmol/L) | Standard Error 0.243 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | -1.74 Millimoles per liter (mmol/L) | Standard Error 0.158 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 | -0.69 Millimoles per liter (mmol/L) | Standard Error 0.159 |
Secondary
Change From Baseline in FPG at Week 104 and Week 156
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.
Time frame: Baseline, Week 104, and Week 156
Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 104, n=12, 128, 103 | 0.43 Millimoles per liter (mmol/L) | Standard Deviation 3.346 |
| Placebo + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 156, n=9, 88, 71 | -0.50 Millimoles per liter (mmol/L) | Standard Deviation 4.093 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 104, n=12, 128, 103 | -1.98 Millimoles per liter (mmol/L) | Standard Deviation 3.471 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 156, n=9, 88, 71 | -1.94 Millimoles per liter (mmol/L) | Standard Deviation 3.127 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 104, n=12, 128, 103 | -0.99 Millimoles per liter (mmol/L) | Standard Deviation 3.083 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in FPG at Week 104 and Week 156 | Week 156, n=9, 88, 71 | -0.88 Millimoles per liter (mmol/L) | Standard Deviation 2.652 |
Secondary
Change From Baseline in HbA1c at Week 104 and Week 156
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 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.
Time frame: Baseline, Week 104, and Week 156
Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 104, n=12, 130, 104 | -0.32 Percentage of HbA1c in the blood | Standard Deviation 0.552 |
| Placebo + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 156, n=9, 89, 71 | -0.10 Percentage of HbA1c in the blood | Standard Deviation 0.923 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 104, n=12, 130, 104 | -1.09 Percentage of HbA1c in the blood | Standard Deviation 1.119 |
| Pioglitazone + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 156, n=9, 89, 71 | -0.97 Percentage of HbA1c in the blood | Standard Deviation 1.063 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 104, n=12, 130, 104 | -0.76 Percentage of HbA1c in the blood | Standard Deviation 1.009 |
| Albiglutide + Metformin + Glimepiride | Change From Baseline in HbA1c at Week 104 and Week 156 | Week 156, n=9, 89, 71 | -0.46 Percentage of HbA1c in the blood | Standard Deviation 1.113 |
Secondary
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156
The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 156) was assessed.
Time frame: Week 156
Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed. This analysis used observed HbA1c values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.0% | 3 Participants |
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <6.5% | 1 Participants |
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.5% | 5 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.0% | 44 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <6.5% | 23 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.5% | 68 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <6.5% | 16 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.5% | 45 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 | HbA1c <7.0% | 26 Participants |
Secondary
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52
The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5%, \<7%, and \<7.5% at Week 52) was assessed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 52.
Time frame: Week 52
Population: ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.5% | 19 Participants |
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.0% | 10 Participants |
| Placebo + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <6.5% | 4 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.5% | 150 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <6.5% | 37 Participants |
| Pioglitazone + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.0% | 94 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.0% | 79 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <6.5% | 27 Participants |
| Albiglutide + Metformin + Glimepiride | Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 | HbA1c <7.5% | 126 Participants |
Secondary
Time to Hyperglycemia Rescue
Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia 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 weeks.
Time frame: From the start of study medication until the end of the treatment (up to Week 156)
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Metformin + Glimepiride | Time to Hyperglycemia Rescue | 49.57 Weeks |
| Pioglitazone + Metformin + Glimepiride | Time to Hyperglycemia Rescue | NA Weeks |
| Albiglutide + Metformin + Glimepiride | Time to Hyperglycemia Rescue | 137.71 Weeks |