Prader-Willi syndrome (PWS) is a rare and complex genetic disorder characterised by physical, behavioural, and cognitive challenges. While infants with PWS often present with poor muscle tone, weak sucking ability, and feeding difficulties, older children and adults may struggle with hormone deficiencies, sleep abnormalities, and delayed development. 1 Individuals with PWS lack normal signals of satiety and have a chronic feeling of hunger (hyperphagia). They are usually unable to
control their food intake and will overeat if not closely monitored, frequently leading to development of severe obesity and its many complications (Figure 1). The development of glucagon-like peptide 1 receptor agonists (GLP1-RA) as potent anti-obesity medications, in addition to their effects on type 2 diabetes, has led to interest in their potential to mitigate the hyperphagia in PWS in the hope of leading to weight loss and a diminished need for surveillance of food availability
by parents and carers. Unfortunately, there is a lack of high-quality evidence for the efficacy and safety of GLP1-RAs in individuals with PWS. Randomised controlled trials of exenatide3 and liraglutide4 in individuals with PWS showed modest effects on hyperphagia, but they found no statistical or clinically significant effect on body weight. A search of US, UK and European trial registries in August 2025 shows no registered trials of semaglutide in PWS. A recent metaanalysis concluded that despite a high unmet need, ‘existing obesity and diabetes assets are not effective for genetic obesity such as PWS’.5 Despite this, the newer semaglutide (a weekly GLP-1 agonist) and tirzepatide (a dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide [GIP]) are increasingly being prescribed to individuals with PWS with little consensus about their efficacy and safety. Given the high rate of significant gastrointestinal complications in PWS, including chronic constipation, intestinal blockage and delayed gastric emptying, as well as an increased pain threshold, individuals with PWS may be at higher risk for some adverse events associated with the use of GLP-1RAs. In addition, many new drugs targeting different
pathways relevant to the pathophysiology of PWS are in development,6 and agreement on an optimal data set to assess their
efficacy and safety within and without clinical trials would be valuable. To address these issues, the Foundation for Prader-Willi Research (FPWR) convened a clinical workshop linked to the clinical and scientific sessions at the recent United in Hope: International Prader-Willi Syndrome Conference (IPWSO).7