Effect of Exenatide on Fat Deposition and a Metabolic Profile in Patients with Metabolic Syndrome Manuel Gonza ´ lez-Ortiz, M.D., M.Sc., Ph.D., Esperanza Martı ´nez-Abundis, M.D., M.Sc., Ph.D., Jose ´ A. Robles-Cervantes, M.D., M.Sc., Ph.D., and Maria G. Ramos-Zavala, M.D., M.Sc., Ph.D. Abstract Background: The aim of this study was to evaluate the effect of exenatide on fat deposition and a metabolic profile in patients with metabolic syndrome. Methods: An uncontrolled, open clinical study was carried out in 10 patients with metabolic syndrome and without pharmacological treatment. Patients received exenatide (5 mg) subcutaneously twice daily for 1 month. Before and after the intervention, metabolic profile and phases of insulin secretion and insulin sensitivity were estimated. To assess insulin secretion and sensitivity, the hyperglycemic–hyperinsulinemic clamp technique was performed. Computed tomography was performed to evaluate both subcutaneous and visceral fat. The Wil- coxon signed-rank test and Mann–Whitney U-test were used for statistical analyses. Results: Weight, body mass index, waist circumference, and systolic blood pressure were decreased by ex- enatide. Subcutaneous fat deposition decreased by 4.4% compared to the basal value. There were significant decreases in total cholesterol and low-density lipoprotein cholesterol, as well as an increment in the first phase of insulin secretion after the intervention. Conclusion: One-month administration of exenatide significantly decreased subcutaneous fat deposition by 4.4%, improving the metabolic profile in patients with metabolic syndrome. Introduction T ype 2 diabetes mellitus (T2DM), frequently associated with obesity, has become a worldwide health problem with a significant impact due to its high prevalence and to complications that decrease patients’ quality of life and life expectancy. There is a major deterioration in the family economy and also a major economic burden on health in- stitutions that treat these problems. 1 Several guidelines and algorithms for the medical management of T2DM have been proposed in the medical literature. One recently published study includes exenatide as an option to reach the goals of metabolic control because of its promising results. 2 Exenatide is a synthetic exendin-4 that shares 53% amino acid sequence identity with human glucagon-like peptide-1 (GLP-1), an incretin, and binds directly to GLP-1 receptors. Clinical studies have shown improvements in first- and second-phase glucose-stimulated insulin secretion, suppres- sion of glucagon secretion, and slowing gastric motility. These studies in patients with T2DM demonstrate improve- ment of glycemic control accompanied by a reduction in body weight. 3 However, the effect of exenatide on fat de- position in humans has not yet been established. Metabolic syndrome is a cluster of endocrine disturbances including obesity, dysglycemia, dyslipidemia, and hyper- tension predisposing individuals to increased risk for ath- erosclerosis, cardiovascular events, and eventually T2DM. 4 The International Diabetes Federation (IDF) has proposed waist circumference (WC) to be included among their criteria and, as the principal condition, to diagnose metabolic syn- drome. 5 Exenatide has improved anthropometric parameters and cardiometabolic risk factors in patients with metabolic syndrome. 6 The aim to this study was to evaluate the effect of exenatide on fat deposition and the metabolic profile in patients with metabolic syndrome. Subjects and Methods An uncontrolled, open clinical trial was carried out in 10 nondiabetic patients (20–40 years of age) with newly diagnosed Cardiovascular Research Unit, Physiology Department, Health Science University Center, University of Guadalajara and Medical Research Unit in Clinical Epidemiology, Specialties Hospital, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico. METABOLIC SYNDROME AND RELATED DISORDERS Volume 9, Number 1, 2011 ª Mary Ann Liebert, Inc. Pp. 31–34 DOI: 10.1089/met.2010.0025 31