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

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-656
Parisa Salehi*1, Steven D Mittelman2, Mitchell E. Geffner3 and Debra Devoe Jeandron3
1Children's Hospital of Los Angeles, Los Angeles, CA, 2Childrens Hospital Los Angeles, Los Angeles, CA, 3Children's Hospital Los Angeles, Los Angeles, CA
Background: Obesity is a major source of morbidity and mortality in patients with Prader-Willi Syndrome (PWS) and for which there is no effective medical therapy. PWS is associated with central hyperphagia and an abnormal gut hormone profile, most notably, hyperghrelinemia. As hyperphagia seems to be the primary basis of obesity in PWS, a therapy targeting appetite could potentially be an effective treatment. Exenatide [Byetta (synthetic exendin-4); Amylin Pharmaceuticals, San Diego, CA] is a GLP-1 receptor agonist that causes reduced appetite and weight loss, which is believed to be, in part, centrally mediated. In addition, animal studies have shown that exendin-4 decreases ghrelin levels. Thus, exenatide could possibly improve the hyperphagia and obesity in patients with PWS.

Objective: To determine the effect of a 6-month trial of exenatide on appetite and weight in youth with PWS.

Methods: Ten overweight subjects with PWS (13-25 years) were recruited for an open-label, non-randomized, 6-month longitudinal exenatide trial starting at a dose of 5 mcg SQ BID with an increase to 10 mcg SQ BID after 1 month. Primary outcome measures were weight, BMI, body composition, appetite, and serum measurements of gut hormones, including acylated ghrelin. Subjects were followed with appetite questionnaires, meal tolerance tests, DEXA scans, and anthropometrics. No dietary modifications were made during the study. Data are presented as mean + SD and differences between groups assessed by paired t-tests. In addition, drug safety was closely monitored.

Results: Preliminary analyses show that total appetite scores significantly decreased from 29.6 ± 6.42 to 24.78 ± 7.50 after 1 month of exenatide (p=0.002) and to 19.33 ± 8.43 after 3 months of treatment (p=0.015). However, no significant changes in weight or BMI were noted from baseline after 1 month (weight +0.63 ± 1.49 kg, p=0.24; BMI +0.13 ± 0.84 kg/m2, p=0.66) or 3 months (weight +1.52 ± 2.95 kg, p=0.26; BMI +0.36 ± 1.00 kg/m2, p=0.42) of treatment. Analysis of gut hormones is pending batch analysis. Exenatide was well-tolerated without major adverse effects. 

Conclusion: Exenatide appears to be safe and effective in decreasing appetite in youth with PWS, although it did not decrease 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 used in conjunction with behavioral modification.

Nothing to Disclose: PS, SDM, MEG, DDJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH NCRR CTSI GRANT 1UL1RR031986;  Amylin Pharmaceuticals for drug support; Children's Hospital of Los Angeles, Department of Endocrinology