2008 Grant Award - Aaron S. Kelly, Ph.D.

GLP-1 Therapy for Weight Loss and Improved Glucose Tolerance in Obese Children: A Randomized, Controlled Pilot Study

Aaron S. Kelly, Ph.D.
Department of Pediatrics, University of Minnesota

Behavioral therapy should be the foundational approach to treating obesity and impaired glucose tolerance (IGT) in children. However, many children are unable to alter their lifestyle sufficiently and may benefit from medical therapy to facilitate weight loss and improve glucose metabolism. Few drug therapies for weight loss exist for children and novel options should be explored. Exenatide is a new glucagon like peptide-1 (GLP-1) agonist that reduces postprandial glucose excursions and reduces body weight through its ability to slow gastric emptying and by suppressing appetite. Importantly, the weight loss effects with exenatide are progressive and sustained over a period of at least 2 years. Our primary aim is to examine the effects of 6 months of exenatide treatment on body weight, body mass index (BMI), waist circumference, body composition, and glucose tolerance in obese children with IGT. Our secondary aim is to examine the effects of exenatide treatment on arterial endothelial function and stiffness, blood biomarkers of endothelial activation, and adipokines in obese children with IGT. To accomplish these aims, we will enroll 20 obese children and adolescents into a randomized, single-blind, controlled clinical trial. Patients will be randomly assigned to exenatide (n = 10) or usual care (n = 10) for 6 months in addition to background behavioral therapy through the UMN Pediatric Weight Management Program. This multidisciplinary pilot study will result in the acquisition of valuable preliminary data which will be used to seek funding for and conduct a larger-scale clinical trial evaluating the safety and efficacy of GLP-1 therapy for weight loss and improved glucose tolerance in obese children with IGT.