ESPE Abstracts (2015) 84 P-2-377

The Effect of Exenatide on Weight and Appetite in Overweight Adolescents and Young Adults with Prader-Willi Syndrome

Parisa Salehia, Isabel Hsub, Colleen G Azenc, Steven D Mittelmand, Mitchell E Geffnerd & Debra Jeandrone


aDivision of Endocrinology, Seattle Children’s Hospital, University of Washington, Seattle, Washington, USA; bCenter for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, Los Angeles, California, USA; cKeck School of Medicine, Clinical and Translational Science Institute (CTSI), The Saban Research Institute, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA; dKeck School of Medicine, The Saban Research Institute, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital of Los Angeles, University of Southern California, Los Angeles, California, USA; eKeck School of Medicine, Center for Endocrinology, Diabetes and Metabolism, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA


Background: Prader–Willi Syndrome (PWS) is a genetic disorder associated with hyperphagia and hyperghrelinemia with major morbidity due to obesity. The aetiology of hyperphagia is unknown, but presumed to be multifactorial, and, as ghrelin is orexigenic, high levels may contribute to weight issues in PWS. Currently, there is no effective medical treatment for hyperphagia in PWS, but targeting appetite could be beneficial. Exenatide (Byetta (synthetic exendin-4); AstraZeneca) is a GLP1 receptor agonist which reduces appetite and weight. In rodent studies, exendin-4 decreased ghrelin levels. Thus, exenatide may be an effective treatment in PWS.

Objective and hypotheses: The objective of this pilot study was to determine the effect of a 6-month trial of exenatide on appetite, weight, and gut hormones in youth with PWS.

Method: Ten overweight or obese subjects with PWS (13–25 years) were recruited for an open-label, non-randomized, 6-month longitudinal study using standard exenatide dosing. Primary outcomes were weight, BMI, truncal fat, appetite, and acylated (active) ghrelin at 0,1, 3, and 6 months and during mixed meal tolerance tests (MMTT) at 0 and 6 months. A syndrome-validated appetite questionnaire, DXAs, anthropometrics, and metabolic markers were assessed. Consistent caregivers completed questionnaires with possible scores between 11 and 55 (higher values=higher appetites). No dietary modifications were made. Data are presented as mean±S.D. and within-subject changes between visits were analysed by mixed model repeated measures.

Results: Total appetite scores significantly decreased from baseline (32.2±8.7) after 1, 3, and 6 months of treatment (27.5±8.8, 25.4±9.3, and 25.4±7.2, respectively; P=0.004). However, there were no significant changes in weight, BMI Z-score, or truncal fat. There was no significant change in fasting or ghrelin excursion during MMTT based on area under the curve data. There were no significant adverse events.

Conclusion: Exenatide was safe and effective in decreasing appetite in youth with PWS, without decreases in weight or BMI in the short term. Larger, controlled, longer-term trials are needed to confirm the safety and efficacy of exenatide, and to evaluate whether its use might induce weight loss when given in conjunction with behavioral modification.

Funding: Department of Endocrinology, Children’s Hosptial Los Angeles (CHLA) Merit Fund (8030-RR1000019-00, $30,000, 2011), NIH NCRR CTSI grant (1UL1RR031986, $10,000, 2011), and Amylin Pharmaceuticals (now AstraZeneca) (2011-E-0389, drug only, 2011).

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