Effect of Exenatide on Abdominal Fat Distribution in Patients With Type 2 Diabetes Pretreated With Metformin

Study Overview
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Brief Summary
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A multicenter, randomized, double-blind, placebo-controlled trial will assess the effects of twice-daily subcutaneous injection with exenatide versus treatment with matching placebo injection on abdominal visceral fat content.

Official Title
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Effect of Exenatide on Abdominal Fat Distribution in Patients With Type 2 Diabetes Pretreated With Metformin

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: placebo
* Drug: exenatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 85 years of age, inclusive. Patients with type 2 diabetes Patients have been treated with metformin, at a stable dose for at least 3 months prior to Visit 1 Patients have HbA1c of 7.0% to 8.9%, inclusive. Patients have a body mass index >27 kg/m2 and <40 kg/m2 and meet local CT scan body weight requirements. For South Asian, Japanese, and Chinese patients, a body mass index >=25 kg/m2 is acceptable as the lower limit. Patients have a history of stable body weight (not varying by >2 kg in the 3 months prior to Visit 1). Medications for the treatment of high blood pressure are stable with respect to treatment regimen for 4 weeks prior to Visit 1. Stable regimen of lipid-lowering agents for 6 weeks prior to Visit 1. Exclusion Criteria: Have received treatment in the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Have an 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 a history of renal transplantation, or are currently receiving renal dialysis. Have had a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year prior to Visit 1, 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 known hemoglobinopathy or clinically significant, chronic anemia. Known or are likely to become transfusion dependent during the study. Have active, symptomatic proliferative retinopathy. Are receiving chronic treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility. (i.e. metoclopramide, cisapride, and chronic use of macrolide antibiotics) Have severe gastrointestinal disease, including gastroparesis. Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 months immediately prior to Visit 1. Have taken exenatide, liraglutide or any other GLP-1 receptor agonist in the past 6 months, either in a clinical study or as commercially available medication. Patients with known allergy to exenatide should be excluded. Have used any prescription or over the counter drug to promote weight loss within 3 months prior to Visit 1, or intend to use such a drug during the study. (Examples: Xenical [orlistat], Meridia [sibutramine], Acutrim [phenylpropanolamine], Acomplia [rimonabant]). Have participated in a structured weight loss program within 3 months prior to Visit 1, or intend to participate in such a plan during this study. Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to Visit 1: Insulin; Thiazolidinediones; Alpha-glucosidase inhibitors; Sulfonylureas; Oral DPP-IV inhibitors; Meglitinides. Are taking warfarin, or a coumarol derivative.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: placebo<br>* subcutaneous injection, twice a day<br>|
| Experimental: 2<br> | Drug: exenatide<br>* subcutaneous injection, twice a day, 10mcg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Abdominal Visceral Fat From Baseline to 6 Months | Percentage change in abdominal visceral fat | baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Total Abdominal Fat From Baseline to 6 Months | Percentage change in total abdominal fat | baseline, 6 months | 
| Percentage Change in Subcutaneous Abdominal Fat From Baseline to 6 Months | Percentage change in subcutaneous abdominal fat | baseline, 6 months | 
| Change in HbA1c From Baseline to 6 Months | Change in HbA1c from baseline to 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated. | baseline, 6 months | 
| Percentage of Patients With HbA1c <=7.0% at 6 Months | Percentage of patients with HbA1c values <= 7.0% measured at 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated. | 6 months | 
| Change in Fasting Plasma Glucose From Baseline to 6 Months | Change in Fasting plasma glucose | baseline, 6 months | 
| Change in Weight From Baseline to 6 Months | Change in weight | baseline, 6 months | 
| Change in Systolic Blood Pressure From Baseline to 6 Months | Change in Systolic blood pressure | baseline, 6 months | 
| Change in Diastolic Blood Pressure From Baseline to 6 Months | Change in Diastolic blood pressure | baseline, 6 months | 
| Change in Total Cholesterol From Baseline to 6 Months | Change in total cholesterol | baseline, 6 months | 
| Change in Triglycerides From Baseline to 6 Months | Change in triglycerides | baseline, 6 months | 
| Change in High-Density Lipoprotein (HDL) Cholesterol From Baseline to 6 Months | Change in HDL cholesterol | baseline, 6 months | 
| Assessment of Event Rate of Treatment- Emergent Hypoglycemic Event | All hypoglycemia episodes defined as major (results in loss of consciousness, seizure or coma resolving after administration of glucagon or glucose OR needing third-party assistance to resolve due to severe impairment in consciousness and associated with glucose concentration < 2.8 mol/L.) or minor (non-major event with symptoms consistent with hypoglycemia and glucose value < 2.8 mmol/L prior to treating) or symptoms of hypoglycemia (does not meet the criteria for a major or minor event). | baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus, Amylin, Lilly