Effect on Weight Loss of Exenatide Versus Placebo

Study Overview
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Brief Summary
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This trial is designed to compare the effects of twice-daily exenatide and twice-daily placebo on weight loss. This trial will evaluate overweight and obese subjects with type 2 diabetes who have inadequate glycemic control with metformin, sulfonylurea, or metformin plus a sulfonylurea. Subjects will be treated with exenatide or placebo in addition to their current oral antidiabetes agent regimen and participate in a lifestyle modification program.

Official Title
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Effect on Weight Loss of Exenatide Versus Placebo in Subjects With Type 2 Diabetes Participating in a Lifestyle Modification Program

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes for at least 6 months Have been treated with a stable dose of the following for at least 6 weeks prior to screening: *immediate or extended release metformin, or *a sulfonylurea, or *a fixed-dose sulfonylurea/metformin combination therapy Have an HbA1c of 6.6% to 10.0%, inclusive Have a Body Mass Index (BMI) of 25 kg/m^2 to 39.9 kg/m^2, inclusive Exclusion Criteria: Are treated with any of the following excluded medications: *exogenous insulin, thiazolidinedione, or alpha-glucosidase inhibitor for more than 1 week within 6 weeks of screening; *Symlin injection at any time; * Byetta injection within 3 months of screening or discontinuation of therapy at any time due to adverse reaction; *drugs that directly affect gastrointestinal motility; *use of a weight loss drug (including those available over the counter) within 3 months of screening; *chronic (lasting longer than 2 weeks) systemic corticosteroids (excluding topical, intranasal, and inhaled preparations) by oral, intravenous, or intramuscular route within 2 months of screening Have conditions contraindicating metformin and/or sulfonylurea use Have had a change in lipid-lowering agents within 6 weeks of screening Have received glucagon-like peptide-1 (GLP-1) analogs, or dipeptidyl peptidase-IV inhibitors (DPP-IV inhibitors) or have previously participated in this study 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Group A<br> | Drug: exenatide<br>* subcutaneous injection, 5mcg or 10mcg, twice a day<br>* Other names: Byetta;|
| Placebo Comparator: Group B<br> | Drug: placebo<br>* subcutaneous injection, volume equivalent to exenatide dose, twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Body Weight | Change in body weight from baseline (Week 0) after 24 weeks of treatment (i.e., weight at week 24 minus weight at week 0). Body weight measured in kilograms (k). | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | Change in HbA1c from baseline (Week 0) after 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0). HbA1c is measured as percent (%) of hemoglobin. | baseline, Week 24 | 
| Change From Baseline in 6-point Self Monitored Blood Glucose (SMBG) Profile at Week 24 | Change in SMBG at each of 6 time points throughout a day (blood glucose measurements before and 2 hours after the start of the morning, mid-day, and evening meals); week 24 compared to week 0 (i.e., SMBG at week 24 minus SMBG at week 0). Fasting Glucose measured in millimoles per liter (mmol/L). | baseline, Week 24 | 
| Change From Baseline in Waist Circumference at Week 24 | Change in waist circumference from baseline after 24 weeks of treatment (i.e., waist circumference at week 24 minus waist circumference at week 0). Waist measured in centimeters (cm). | baseline, Week 24 | 
| Ratio of Homeostatic Model Assessment-Beta Cell (HOMA-B) at Week 24 to HOMA-B at Baseline | Ratio of HOMA-B at Week 24 to HOMA-B at baseline (Week 0). HOMA-B is a computer solved model used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency. HOMA-B allows a quantitative assessment of the contributions of deficient beta cell function to the fasting hyperglycemia. HOMA-B is measured as a percent of the normal population (normal beta cell function = 100%, which is used as a reference in the calculation). The higher the percent the better for the participant. | baseline, Week 24 | 
| Ratio of Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) at Week 24 to HOMA-S at Baseline | Ratio of HOMA-S at Week 24 to HOMA-S at baseline, week 0. HOMA-S is a computer solved model used to predict the homeostatic concentrations which arise from varying degrees of insulin sensitivity. HOMA-S allows a quantitative assessment of the contributions of insulin sensitivity to the fasting hyperglycemia. HOMA-S is measured as a percent of the normal population (normal insulin sensitivity = 100%, which is used as a reference in the calculation). The higher the percent the better for the participant. | baseline, Week 24 | 
| Change From Baseline in High Density Lipoprotein (HDL) Cholesterol at Week 24 | Change in HDL cholesterol from baseline after 24 weeks of treatment (i.e., HDL cholesterol at week 24 minus HDL cholesterol at week 0). HDL measured as mmol/L. | baseline, Week 24 | 
| Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Week 24 | Change in LDL cholesterol from baseline (Week 0) after 24 weeks of treatment (ie., LDL cholesterol at week 24 minus LDL cholesterol at week 0). LDL cholesterol measured in mmol/L | baseline, Week 24 | 
| Change From Baseline in Total Cholesterol at Week 24 | Change in total cholesterol from baseline after 24 weeks of treatment (i.e., total cholesterol at week 24 minus total cholesterol at week 0). Total cholesterol measured in mmol/L. | baseline, week 24 | 
| Ratio of Triglycerides at Week 24 to Triglycerides at Baseline | Ratio of triglyceride levels at Week 24 to triglyceride levels at baseline, Week 0 (ie., triglycerides at Week 24 divided by triglycerides at baseline, Week 0). Triglycerides measured in mmol/L. | baseline, Week 24 | 
| Number of Participants With Hypoglycemic Events During the Study | Number of participants experiencing one or more events of hypoglycemia at any point in the study | Baseline to 24 weeks | 
| Rate of Hypoglycemic Events | Overall rate of hypoglycemia, adjusted for 1 year (ie., events of hypoglycemia per participant per year). | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, overweight, obesity, weight loss, exenatide, Amylin, Lilly