Endocrine Abstracts

JOINT208

Introduction: Prader-Willi syndrome (PWS) is the most prevalent cause of syndromic obesity. Obesity development in PWS is driven by dysfunction in neural pathways involved in satiety and reward, dysregulation in hormones regulating satiety and food intake, altered body composition and reduced energy expenditure, as well as the presence of various hormone deficiencies. As hyperphagia, satiety dysfunction and consequent food-seeking behaviors are intrinsic to PWS, obesity management can be challenging.

Case series: We present a long-term follow-up of treatment with GLP-1 receptor agonist (GLP-1 RA) semaglutide, up to 37 months, in three patients with PWS without diabetes. Patient 1 was a 28-year-old female with PWS, resulting from uniparental disomy, with BMI 50.8 kg/m². She was initially treated with a calorie-restricted diet and subsequently admitted to a specialized “group home center”, however, her weight continued to progressively increase. Patient 2 was a 39-year-old female with PWS resulting from mosaic maternal uniparental disomy who underwent metabolic surgery at the age of 29, first a gastric band surgery and subsequently Roux-en-Y gastric bypass. Despite an initial weight loss of approximately 50 kg, she ultimately regained most of her lost weight. Before treatment with semaglutide she reached her maximum weight of 174 kg, her BMI was 82.8 kg/m². Patient 23 was a 25-year-old male with PWS, resulting from a uniparental maternal disomy, with body mass index (BMI) 41.3 kg/m². Semaglutide treatment at dosages from 0.5 mg to 2 mg weekly demonstrated variable efficacy, from preventing further weight gain in Patient 1 to achieving weight loss of up to 14.4% and 11% relative to baseline, in Patient 2 and Patient 3, respectively. All patients reported appetite suppression and increased satiety during semaglutide treatment, which was diminished during short term treatment interruptions due to drug unavailability. Mild transient gastrointestinal-related side effects were reported during dose escalation in the case of Patient 2, who had a history of metabolic surgery. No serious adverse events were reported during the observation period.

Conclusions: Following a personalized approach, GLP-1 RAs may have the potential to address the hallmark challenges of hyperphagia, obesity and metabolic dysfunction associated with syndromic obesity in PWS, with mild to moderate efficacy. Future research should prioritize long-term randomized placebo-controlled trials with larger sample sizes to provide stronger evidence on the long-term efficacy and safety of incretin therapies for obesity treatment in PWS as well as explore the potential synergistic effects combined with other therapeutic interventions.