Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3)

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of 2.0 mg exenatide once weekly and insulin glargine, titrated to glucose targets using the algorithm described by Yki- Järvinen et al.(2007), with respect to glycemic improvements, body weight, fasting lipids, safety, and tolerability.

Official Title
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Efficacy of Once-Weekly Exenatide Long-Acting Release and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Exenatide Once Weekly
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has type 2 diabetes and at least 18 years of age at screening. Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening. Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening. Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening). Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening OR Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening and have been treated with SU for at least 3 months and have been taking a stable dose of at least an optimally effective dose of brand of SU for 8 weeks prior to screening. Exclusion Criteria: Have had a clinically significant 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; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study. Have clinical signs or symptoms of liver disease, acute or chronic hepatitis. 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 had greater than three episodes of major hypoglycemia within 6 months prior to screening. Have any contraindication for the oral antidiabetic agent which they use. Have a known allergy or hypersensitivity to insulin glargine, exenatide once weekly, or excipients contained in these agents. Are known to 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 for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: Insulin Thiazolidinediones (e.g., Actos® [pioglitazone] or Avandia® [rosiglitazone]) Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose]) Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]). Byetta® (exenatide BID formulation) Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin]) Symlin® (pramlintide acetate). Have had an organ transplant. Have donated blood within 30 days of screening. Have previously completed or 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Exenatide Once Weekly<br>* subcutaneous injection, 2.0mcg, once weekly<br>|
| Active Comparator: 2<br> | Drug: Insulin Glargine<br>* subcutaneous injection, variable dose, QD<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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <=7.0% at Week 26 | Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline) | Baseline, Week 26 | 
| Percentage of Patients Achieving HbA1c <=6.5% at Week 26 | Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline) | Baseline, Week 26 | 
| Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | Change in FSG (mmol/L) from Baseline to Week 26 | Baseline, Week 26 | 
| Change in Body Weight (BW) From Baseline to Week 26 | Change in BW (kg) from Baseline to Week 26 | Baseline, Week 26 | 
| Change in Total Cholesterol From Baseline to Week 26 | Change in Total Cholesterol (mmol/L) from Baseline to Week 26 | Baseline, Week 26 | 
| Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26 | Change in HDL (mmol/L) from Baseline to Week 26 | Baseline, Week 26 | 
| Ratio of Triglycerides at Week 26 to Baseline | Ratio of Triglycerides (measured in mmol/L) at Week 26 to Baseline. Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline. | Baseline, Week 26 | 
| Change in Blood Pressure From Baseline to Week 26 | Change in Systolic Blood Pressure (mmHg) and Diastolic Blood Pressure (mmHg) from Baseline to Week 26 | Baseline, Week 26 | 
| Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes | Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any time a patient felt that he or she was experiencing a sign or symptom of hypoglycemia that was self-treated or resolved on its own and had a blood glucose level <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. | Baseline to Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide, exenatide once weekly, metformin, sulfonylurea, insulin glargine, Amylin, Lilly