Endocrine Abstracts

JOINT3863

Introduction: At the Dutch Center of Reference for Prader-Willi Syndrome (PWS) we see over 450 children and adults with PWS. One of the most challenging medical problems in PWS is obesity and its complications. In PWS, obesity is multifactorial and caused by both physical factors (low muscle mass, hypotonia, low basal metabolic rate, hormone deficiencies), medication and behavioral factors (hyperphagia). Anti-obesity drugs are thought to attenuate this hypothalamic hyperphagia. In this study, we report the effects of anti-obesity drugs in PWS.

Methods: Retrospective study among 201 young adults and adults with PWS attending the Dutch national reference center for PWS. All patients follow the same trajectory consisting of a medical questionnaire, structured interview, complete physical examination, biochemical measurements and, if needed, imaging. ¹ After screening for medical problems, treatment is started. Since 2024, lifestyle coaching for people with intellectual disabilities has become available in the Netherlands and we have started to prescribe anti-obesity drugs to adults with PWS in our center. In case of obesity (BMI>30), we offer two treatment options:

1. After routine PWS-specific food safety advice, lifestyle coaching for people with intellectual disabilities is started. After participating in this program for one year, anti-obesity drugs are started, reimbursed by the Dutch health insurance.

2. In some patients, caregivers want to start anti-obesity drugs on own costs because lifestyle is already considered optimal and routine PWS-specific food safety measures have already been taken. In that case, the lifestyle intervention program is skipped and anti-obesity drugs like GLP1-agonists (Liraglutide and Semaglutide) and Naltrexon/bupropion are prescribed.

Results: Since the start of this standard obesity approach, we have prescribed anti-obesity drugs to 28 adults with PWS aged 20-56 years. Average percentage of weight loss was 8. 7% (ranging from 0. 9 to 19. 5%) for Liraglutide, 9. 3% (ranging from 2. 9 to 23. 9%) for Semaglutide and 0. 2% (ranging from a weight gain of +3. 1% to a weight loss of 3. 4%) for Naltrexon/bupropion. The single patient on Dulaglutide lost 0. 7% of his weight. Few side effects were reported and no serious gastrointestinal problems were reported.

Conclusion: Anti-obesity drugs can have a beneficial effect on weight in people with PWS. However, the effect is heterogeneous and external control of food intake seems to be more important than the medication.

Reference: 1. Pellikaan K, et al. Missed Diagnoses and Health Problems in Adults With Prader-Willi Syndrome: Recommendations for Screening and Treatment. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4671–87.