GLP-1 Therapy for Weight Loss and Improved Glucose Tolerance in Obese Children

This will be a randomized, open-label, controlled, crossover clinical trial in 12 patients. All patients will receive exenatide and undergo the control phase. Following baseline testing, participants will be randomly assigned to treatment order: therapy (exenatide) or control (lifestyle modification). Half (n = 6) will receive exenatide first (3-months) then cross over to control (no drug therapy for 3-months). Half (n = 6) will be assigned to control first (3-months) then cross over to exenatide (3-months). All efforts will be made to stratify randomization based on gender of the participants. Treatment and control conditions will be three months each. Because of the route of administration of exenatide (subcutaneous injection), placebo will not be utilized for the control phase of the study. Participants in this study will engage in background intensive lifestyle modification offered by the University of Minnesota Pediatric Weight Management Clinic for the entire study, even during the active drug treatment phase. Intensive lifestyle modification will be purely clinical in nature in which children and their families receive continuing counseling from a team of trained professionals including physicians, dieticians, and psychologists to reduce weight by making healthier eating choices and increasing physical activity. The screening visit will take place in the Pediatric Weight Management Clinic and will include a complete medical history and physical examination. Screening will include review of medical records for previous clinical and laboratory data (including clinically-ordered glucose tolerance test results). All research testing will take place in the University of Minnesota General Clinical Research Center (GCRC). Subjects will undergo testing at the following intervals: baseline, immediately after the first 3-month phase (whether exenatide or control), and immediately after the second 3- month phase (whether exenatide or control). The following measures will be collected after the subject has been fasting for at least twelve hours: * Height, weight, body mass index, waist and hip circumference * Fat and lean mass (dual energy x-ray absorptiometry: DXA) * Tanner stage determination (performed during screening physical exam or may be obtained from medical chart) * Fasting lipid profile (total-, LDL-, and HDL-cholesterol, triglycerides) * Systolic and diastolic blood pressure * Oral glucose tolerance test (glucose and insulin measured every 30 minutes for 2 hours) * Endothelial function (digital reactive hyperemia: EndoPAT 2000, Itamar Medical) - in addition to the baseline measure, endothelial function testing will occur at hours one and two of the oral glucose tolerance test * Frozen plasma for storage - in addition to the baseline blood draw, blood for endothelial biomarkers will be obtained at hours one and two of the oral glucose tolerance test * Arterial stiffness (pulse wave velocity; augmentation index: Sphygmocor, AtCor Medical) * Frozen plasma for pharmacokinetic determination of exenatide in children