Exenatide and Weight Loss for Diabetes Prevention

Study Overview
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Brief Summary
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Exenatide, a GLP-1 agonist approved for lowering blood glucose concentrations in patients with type 2 diabetes, has been associated with restoration of the first-phase insulin response when administered intravenously to patients with type 2 diabetes. In longer clinical trials, it is associated with progressive decreases in body weight, and improvement in the dyslipidemia that characterizes insulin resistance, although insulin resistance was not quantified. The investigators will seek to determine whether exenatide would have similar effects in individuals who were not diabetic. in particular, the drug effect on beta cell function and insulin sensitivity would be subject to less confounding by changes in blood glucose in the prediabetic population, allowing for clearer evaluation of the physiological effects of the drug on these metabolic endpoints. The investigators will compare 2 groups of prediabetic insulin resistant individuals, all on a weight loss diet and one group on exenatide and the other on placebo. The investigators will evaluate restoration of first phase insulin response, potential glucose lowering effects, including both reversal of prediabetes and hypoglycemia, and improvement in insulin resistance.

Official Title
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Randomized Trial Investigating Exenatide for Diabetes Prevention in Obese, Insulin-Resistant Individuals With Prediabetes

Conditions
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Pre Diabetes, Insulin Resistance

Intervention / Treatment
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* Drug: Exenatide 5 and 10 mcg 2 times a day
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Men and women, BMI 27-37kgm2, Fasting plasma glucose = or > 100 mg/dL and = or < 99 125m g/dl or a 2 hour post OGTT = > 140 mg/dl or = or < 199 mg/dl Exclusion Criteria: Diabetes, Active cardiac, kidney, liver, pulmonary, or other major organ diseases are cause for exclusion. Other exclusionary criteria include: use of corticosteroids, diet medications, antipsychotic medications, history of eating disorder, history of bariatric surgery, active malignancy, recent weight change of more than 2%, inability to attend follow-up visits, excessive alcohol use, investigator's discretion that it is not in patient's best interest

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: exenatide 5 and 10 mcg 2 times a day<br>Exenatide in addition to weight loss. Starting dose 5 mcg titrate to 10 mcg | Drug: Exenatide 5 and 10 mcg 2 times a day<br> <br> * Other names: Byetta;|
| Placebo Comparator: placebo<br>placebo in addition to weight loss | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-phase insulin response | measured using ivgtt | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose lowering effect | measured by fasting and 2 hr plasma glucose during OGTT | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight loss, insulin resistance, acute insulin response, insulin secretion, prediabetes, exenatide