Type 2 Diabetes Mellitus
Conditions
Keywords
Amylin, Lilly, exenatide once weekly, Byetta, Januvia, sitagliptin, thiazolidinedione
Brief summary
This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione) in drug naive patients with type 2 diabetes treated with diet and exercise.
Interventions
subcutaneous injection, 2mg, once weekly plus placebo oral once daily
DRUGmetformin
oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection
DRUGsitagliptin
oral, 100 mg, daily plus placebo once weekly subcutaneous injection
DRUGpioglitazone
oral, 30-45mg, daily plus placebo once weekly subcutaneous injection
Sponsors
Eli Lilly and Company
AstraZeneca
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
* have type 2 diabetes and are treated with diet and exercise alone. * at least 18 years of age. * HbA1c between 7.1% and 11.0%, inclusive. * Body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive. * Have a history of stable body weight (not varying by \>5% for at least 3 months prior to screening).
Exclusion criteria
* Have history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure, coronary artery bypass surgery, or angioplasty * Have a history of renal transplantation or are currently receiving renal dialysis * Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years. * Have history of severe GI disorder (e.g., gastroparesis) * Have a history of acute or chronic pancreatitis. * Have active proliferative retinopathy. * Have been treated with drugs that promote weight loss (e.g., Xenical®\[orlistat\], Meridia® \[sibutramine\], Acomplia® \[rimonabant\], Acutrim® \[phenylpropanolamine\], or similar over-the-counter medications) within 3 months of screening. * Have been treated with any antidiabetic agent for more than 7 days within 3 months prior to screening. * Have had an organ transplant. * Have previously completed or discontinued study drug in this study, withdrawn from this study or any other study investigating exenatide once weekly. * Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Are currently enrolled in any other clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to Week 26 | Baseline, Week 26 | Change in HbA1c from baseline to Week 26. |
| Percentage of Patients Achieving HbA1c <=7% at Week 26 | Baseline, Week 26 | Percentage of patients achieving HbA1c \<=7% at Week 26 (for patients with baseline HbA1c \>7%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | Baseline, Week 26 | Change in Fasting TC from baseline to Week 26. |
| Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | Baseline, Week 26 | Change in Fasting HDL from baseline to Week 26. |
| Ratio of Fasting Triglycerides at Week 26 to Baseline | Baseline, Week 26 | Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline. |
| Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | Baseline, Week 26 | Change in FSG from baseline to Week 26. |
| Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events | Baseline to Week 26 | Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose \<3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)\*\*2). |
| Change in Systolic Blood Pressure From Baseline to Week 26. | Baseline, Week 26 | Change in Systolic Blood Pressure from baseline to Week 26. |
| Change in Diastolic Blood Pressure From Baseline to Week 26. | Baseline, Week 26 | Change in Diastolic Blood Pressure from baseline to Week 26. |
| Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | Baseline to Week 26 | Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)\*\*2). |
| Change in Body Weight From Baseline to Week 26 | Baseline, Week 26 | Change in Body Weight from baseline to Week 26. |
Countries
Argentina, Belgium, Brazil, Canada, France, Germany, Hungary, India, Israel, Italy, Mexico, Poland, Puerto Rico, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Once Weekly Exenatide once weekly (subcutaneous injection of 2 mg exenatide, once a week) + daily oral placebo | 248 |
| Metformin Metformin (1000 mg/day for 2 weeks, then 1500 mg/day for 2 weeks, then 2000 mg/day for 22 weeks) + weekly subcutaneous placebo injection | 246 |
| Pioglitazone Pioglitazone (30 mg/day for 4 weeks, then 45 mg/day for 22 weeks) + weekly subcutaneous placebo injection | 163 |
| Sitagliptin Sitagliptin (100 mg/day for 26 weeks) + weekly subcutaneous placebo injection | 163 |
| Total | 820 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 6 | 5 | 1 |
| Overall Study | Entry Criteria Not Met | 0 | 2 | 1 | 1 |
| Overall Study | Lack of Efficacy-Loss of Glucose Control | 3 | 3 | 5 | 3 |
| Overall Study | Lost to Follow-up | 4 | 1 | 3 | 4 |
| Overall Study | Physician Decision | 3 | 3 | 2 | 3 |
| Overall Study | Protocol Violation | 5 | 9 | 2 | 5 |
| Overall Study | Withdrawal by Subject | 17 | 9 | 12 | 6 |
Baseline characteristics
| Characteristic | Exenatide Once Weekly | Total | Sitagliptin | Pioglitazone | Metformin |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 31 Participants | 109 Participants | 19 Participants | 28 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 217 Participants | 711 Participants | 144 Participants | 135 Participants | 215 Participants |
| Age, Continuous | 53.7 years STANDARD_DEVIATION 10.91 | 53.7 years STANDARD_DEVIATION 11.02 | 52.3 years STANDARD_DEVIATION 11.05 | 55.3 years STANDARD_DEVIATION 10.96 | 53.7 years STANDARD_DEVIATION 11.08 |
| Glycosylated hemoglobin (HbA1c) | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.19 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.22 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.25 | 8.5 percentage of total hemoglobin STANDARD_DEVIATION 1.24 | 8.6 percentage of total hemoglobin STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 109 Participants | 336 Participants | 69 Participants | 66 Participants | 92 Participants |
| Sex: Female, Male Male | 139 Participants | 484 Participants | 94 Participants | 97 Participants | 154 Participants |
| Weight | 87.5 kg STANDARD_DEVIATION 18.88 | 87.0 kg STANDARD_DEVIATION 18.83 | 88.7 kg STANDARD_DEVIATION 18.65 | 86.1 kg STANDARD_DEVIATION 17.77 | 85.9 kg STANDARD_DEVIATION 19.57 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 109 / 248 | 94 / 246 | 57 / 163 | 55 / 163 |
| serious Total, serious adverse events | 4 / 248 | 12 / 246 | 9 / 163 | 3 / 163 |
Outcome results
Primary
Change in HbA1c From Baseline to Week 26
Change in HbA1c from baseline to Week 26.
Time frame: Baseline, Week 26
Population: Intent to treat (ITT) population consisted of all randomized patients who had taken at least one dose of study drug. All scheduled post-baseline measurements were included in the analysis. Unscheduled visit observations were carried forward to the next scheduled visits.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in HbA1c From Baseline to Week 26 | -1.53 percentage of total hemoglobin | Standard Error 0.07 |
| Metformin | Change in HbA1c From Baseline to Week 26 | -1.48 percentage of total hemoglobin | Standard Error 0.07 |
| Pioglitazone | Change in HbA1c From Baseline to Week 26 | -1.63 percentage of total hemoglobin | Standard Error 0.08 |
| Sitagliptin | Change in HbA1c From Baseline to Week 26 | -1.15 percentage of total hemoglobin | Standard Error 0.08 |
Comparison: Power calculation: A sample of 740 (222 exenatide once weekly, 222 metformin, 148 pioglitazone, and 148 sitagliptin) would provide approximately 90% power to detect a true differences between exenatide once weekly and the 3 comparators: metformin, pioglitazone, and sitagliptin of 0.4%, 0.5%, and 0.5%, respectively in change in HbA1c from baseline to Week 26 with a 2-sided t test at a significance level of 0.05, assuming a common standard deviation of 1.2%.p-value: 0.6298.3% CI: [-0.26, 0.17]Mixed Models Analysis
Comparison: Power calculation: A sample of 740 (222 exenatide once weekly, 222 metformin, 148 pioglitazone, and 148 sitagliptin) would provide approximately 90% power to detect a true differences between exenatide once weekly and the 3 comparators: metformin, pioglitazone, and sitagliptin of 0.4%, 0.5%, and 0.5%, respectively in change in HbA1c from baseline to Week 26 with a 2-sided t test at a significance level of 0.05, assuming a common standard deviation of 1.2%.p-value: 0.32898.3% CI: [-0.15, 0.35]Mixed Models Analysis
Comparison: Power calculation: A sample of 740 (222 exenatide once weekly, 222 metformin, 148 pioglitazone, and 148 sitagliptin) would provide approximately 90% power to detect a true differences between exenatide once weekly and the 3 comparators: metformin, pioglitazone, and sitagliptin of 0.4%, 0.5%, and 0.5%, respectively in change in HbA1c from baseline to Week 26 with a 2-sided t test at a significance level of 0.05, assuming a common standard deviation of 1.2%.p-value: <0.00198.3% CI: [-0.62, -0.13]Mixed Models Analysis
Primary
Percentage of Patients Achieving HbA1c <=7% at Week 26
Percentage of patients achieving HbA1c \<=7% at Week 26 (for patients with baseline HbA1c \>7%).
Time frame: Baseline, Week 26
Population: ITT subjects with baseline HbA1c\>7%. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exenatide Once Weekly | Percentage of Patients Achieving HbA1c <=7% at Week 26 | 64.2 percentage of patients |
| Metformin | Percentage of Patients Achieving HbA1c <=7% at Week 26 | 57.3 percentage of patients |
| Pioglitazone | Percentage of Patients Achieving HbA1c <=7% at Week 26 | 63.3 percentage of patients |
| Sitagliptin | Percentage of Patients Achieving HbA1c <=7% at Week 26 | 45.5 percentage of patients |
p-value: 0.151Fisher Exact
p-value: 0.913Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)\*\*2).
Time frame: Baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
| Metformin | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
| Pioglitazone | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
| Sitagliptin | Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
Secondary
Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events
Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose \<3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)\*\*2).
Time frame: Baseline to Week 26
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events | 0.05 events per subject-year | Standard Error 0.021 |
| Metformin | Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
| Pioglitazone | Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
| Sitagliptin | Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events | 0.00 events per subject-year | Standard Error 0 |
Secondary
Change in Body Weight From Baseline to Week 26
Change in Body Weight from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Body Weight From Baseline to Week 26 | -2.04 kg | Standard Error 0.21 |
| Metformin | Change in Body Weight From Baseline to Week 26 | -2.00 kg | Standard Error 0.21 |
| Pioglitazone | Change in Body Weight From Baseline to Week 26 | 1.52 kg | Standard Error 0.26 |
| Sitagliptin | Change in Body Weight From Baseline to Week 26 | -0.76 kg | Standard Error 0.26 |
Comparison: Change in Body Weight from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline body weight, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.89295% CI: [-0.61, 0.53]Mixed Models Analysis
Comparison: Change in Body Weight from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline body weight, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: <0.00195% CI: [-4.21, -2.9]Mixed Models Analysis
Comparison: Change in Body Weight from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline body weight, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: <0.00195% CI: [-1.92, -0.63]Mixed Models Analysis
Secondary
Change in Diastolic Blood Pressure From Baseline to Week 26.
Change in Diastolic Blood Pressure from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Diastolic Blood Pressure From Baseline to Week 26. | -0.50 mmHg | Standard Error 0.51 |
| Metformin | Change in Diastolic Blood Pressure From Baseline to Week 26. | -0.86 mmHg | Standard Error 0.5 |
| Pioglitazone | Change in Diastolic Blood Pressure From Baseline to Week 26. | -2.50 mmHg | Standard Error 0.63 |
| Sitagliptin | Change in Diastolic Blood Pressure From Baseline to Week 26. | -0.45 mmHg | Standard Error 0.62 |
Comparison: Change in Diastolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline diastolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.6195% CI: [-1.02, 1.73]Mixed Models Analysis
Comparison: Change in Diastolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline diastolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.01395% CI: [0.43, 3.58]Mixed Models Analysis
Comparison: Change in Diastolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline diastolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.94695% CI: [-1.6, 1.49]Mixed Models Analysis
Secondary
Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26
Change in Fasting HDL from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | 0.01 mmol/L | Standard Error 0.01 |
| Metformin | Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | 0.07 mmol/L | Standard Error 0.01 |
| Pioglitazone | Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | 0.17 mmol/L | Standard Error 0.02 |
| Sitagliptin | Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | 0.04 mmol/L | Standard Error 0.02 |
Comparison: Change in Fasting HDL from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline HDL, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.00495% CI: [-0.09, -0.02]Mixed Models Analysis
Comparison: Change in Fasting HDL from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline HDL, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: <0.00195% CI: [-0.19, -0.11]Mixed Models Analysis
Comparison: Change in Fasting HDL from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline HDL, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.14295% CI: [-0.07, 0.01]Mixed Models Analysis
Secondary
Change in Fasting Serum Glucose (FSG) From Baseline to Week 26
Change in FSG from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | -2.25 mmol/L | Standard Error 0.14 |
| Metformin | Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | -1.98 mmol/L | Standard Error 0.14 |
| Pioglitazone | Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | -2.57 mmol/L | Standard Error 0.18 |
| Sitagliptin | Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | -1.13 mmol/L | Standard Error 0.18 |
Comparison: Change in FSG from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline FSG, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.15595% CI: [-0.66, 0.1]Mixed Models Analysis
Comparison: Change in FSG from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline FSG, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.15395% CI: [-0.12, 0.75]Mixed Models Analysis
Comparison: Change in FSG from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline FSG, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: <0.00195% CI: [-1.56, -0.68]Mixed Models Analysis
Secondary
Change in Fasting Total Cholesterol (TC) From Baseline to Week 26
Change in Fasting TC from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | -0.24 mmol/L | Standard Error 0.06 |
| Metformin | Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | -0.22 mmol/L | Standard Error 0.06 |
| Pioglitazone | Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | 0.09 mmol/L | Standard Error 0.08 |
| Sitagliptin | Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | -0.01 mmol/L | Standard Error 0.08 |
Comparison: Change in Fasting TC from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline TC, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.87395% CI: [-0.18, 0.15]Mixed Models Analysis
Comparison: Change in Fasting TC from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline TC, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: <0.00195% CI: [-0.52, -0.14]Mixed Models Analysis
Comparison: Change in Fasting TC from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline TC, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.02295% CI: [-0.41, -0.03]Mixed Models Analysis
Secondary
Change in Systolic Blood Pressure From Baseline to Week 26.
Change in Systolic Blood Pressure from baseline to Week 26.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. All scheduled post-baseline measurements were included in the analysis, with no imputation of missing data other than that inherent in the MMRM model was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Change in Systolic Blood Pressure From Baseline to Week 26. | -1.25 mmHg | Standard Error 0.79 |
| Metformin | Change in Systolic Blood Pressure From Baseline to Week 26. | 0.14 mmHg | Standard Error 0.78 |
| Pioglitazone | Change in Systolic Blood Pressure From Baseline to Week 26. | -1.74 mmHg | Standard Error 0.98 |
| Sitagliptin | Change in Systolic Blood Pressure From Baseline to Week 26. | -1.81 mmHg | Standard Error 0.96 |
Comparison: Change in Systolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline systolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.20195% CI: [-3.52, 0.74]Mixed Models Analysis
Comparison: Change in Systolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline systolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.69395% CI: [-1.94, 2.93]Mixed Models Analysis
Comparison: Change in Systolic Blood Pressure from baseline to Week 26 was analyzed using an MMRM ANCOVA model with treatment, baseline systolic blood pressure, country, week of visit, and treatment-by week interaction as fixed effects; and patient and error as random effects.p-value: 0.64695% CI: [-1.84, 2.96]Mixed Models Analysis
Secondary
Ratio of Fasting Triglycerides at Week 26 to Baseline
Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline.
Time frame: Baseline, Week 26
Population: ITT population. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis. Missing data at endpoint was imputed using LOCF approach.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Exenatide Once Weekly | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.98 ratio | Standard Error 0.03 |
| Metformin | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.96 ratio | Standard Error 0.03 |
| Pioglitazone | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.85 ratio | Standard Error 0.03 |
| Sitagliptin | Ratio of Fasting Triglycerides at Week 26 to Baseline | 0.94 ratio | Standard Error 0.04 |
Comparison: Fasting triglycerides data were logarithm-transformed and the change at Week 26 to baseline, expressed as the ratio, was analyzed using ANCOVA model with treatment and country as factors and baseline triglycerides as a covariate.p-value: 0.65795% CI: [0.94, 1.1]ANCOVA
Comparison: Fasting triglycerides data were logarithm-transformed and the change at Week 26 to baseline, expressed as the ratio, was analyzed using ANCOVA model with treatment and country as factors and baseline triglycerides as a covariate.p-value: 0.00295% CI: [1.06, 1.27]ANCOVA
Comparison: Fasting triglycerides data were logarithm-transformed and the change at Week 26 to baseline, expressed as the ratio, was analyzed using ANCOVA model with treatment and country as factors and baseline triglycerides as a covariate.p-value: 0.39895% CI: [0.95, 1.14]ANCOVA