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

Abstract

Background

Prader-Willi Syndrome (PWS) is associated with hyperphagia and hyperghrelinemia with major morbidity due to obesity without effective medical treatment targeting hyperphagia. Exenatide [Byetta (synthetic Exendin-4); AstraZeneca, Wilmington DE] is a GLP-1 receptor agonist which reduces appetite and weight, and may be an effective treatment in PWS.

Objective

To determine the effect of a 6-mo trial of exenatide on appetite, weight, and gut hormones in youth with PWS.

Methods

Ten overweight and obese subjects with PWS (13-25 yr) were recruited for a 6-mo open-label, non-randomized, longitudinal study conducted at Children's Hospital Los Angeles. Exenatide was given using standard diabetes dosing without dietary modifications. Weight, BMI, truncal fat, appetite, and plasma acylated ghrelin were measured over 6 mo. Mixed meal tolerance tests were done at 0 and 6 mo.

Results

Appetite scores significantly decreased from baseline (32.2 ± 8.7) after 1, 3, and 6 mo of treatment (27.5 ± 8.8, 25.4 ± 9.3, 25.4 ± 7.2, respectively; p=0.004). Hemoglobin A1c decreased significantly after treatment, but weight, BMI z-score, and adiposity did not. There was no significant change in ghrelin.

Conclusion

This is the first longitudinal investigation of the effects of exenatide in subjects with PWS. It was effective in decreasing appetite, without change in weight or BMI in the short term. Larger, controlled, longer-term trials in patients with PWS are needed to confirm the efficacy and safety of exenatide, and to evaluate whether its use might induce weight loss when given in conjunction with behavioral modification.