Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: metformin
* Drug: sitagliptin
* Drug: pioglitazone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide Once Weekly<br> | Drug: exenatide once weekly<br>* subcutaneous injection, 2mg, once weekly plus placebo oral once daily<br>|
| Active Comparator: Metformin<br> | Drug: metformin<br>* oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection<br>|
| Active Comparator: Sitagliptin<br> | Drug: sitagliptin<br>* oral, 100 mg, daily plus placebo once weekly subcutaneous injection<br>|
| Active Comparator: Pioglitazone<br> | Drug: pioglitazone<br>* oral, 30-45mg, daily plus placebo once weekly subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 26 | Change in HbA1c from baseline to Week 26. | Baseline, Week 26 | 
| Percentage of Patients Achieving HbA1c <=7% at Week 26 | Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%). | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | Change in FSG from baseline to Week 26. | Baseline, Week 26 | 
| Change in Body Weight From Baseline to Week 26 | Change in Body Weight from baseline to Week 26. | Baseline, Week 26 | 
| Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 | Change in Fasting TC from baseline to Week 26. | Baseline, Week 26 | 
| Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 | Change in Fasting HDL from baseline to Week 26. | Baseline, Week 26 | 
| 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. | Baseline, Week 26 | 
| 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). | Baseline to Week 26 | 
| 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). | Baseline to Week 26 | 
| Change in Systolic Blood Pressure From Baseline to Week 26. | Change in Systolic Blood Pressure from baseline to Week 26. | Baseline, Week 26 | 
| Change in Diastolic Blood Pressure From Baseline to Week 26. | Change in Diastolic Blood Pressure from baseline to Week 26. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amylin, Lilly, exenatide once weekly, Byetta, Januvia, sitagliptin, thiazolidinedione