Prader–Willi Syndrome (PWS) is the most prevalent cause of syndromic obesity, estimated to affect 1 in 10,000 to 1 in 30,000 newborns. It arises due to the absence of gene expression from the paternal origin within the 15q11-q13 chromosomal region. Approximately 65–75% of cases result from a deletion (type I and type II), while maternal uniparental disomy accounts for 20–30%, and an imprinting defect account for 1–3%.1 PWS is characterized by persistent neonatal hypotonia, short stature due to growth hormone deficiency, hypogonadism, varying degrees of intellectual disability, and hyperphagia starting in early childhood (before the age of 5), leading to severe obesity.2, 3, 4 Obesity is the primary cause of increased morbidity and mortality in individuals with this syndrome. Diabetes typically manifests in 10–25% of PWS patients, typically during adulthood. Paradoxically, despite severe obesity, relative hypoinsulinemia is frequently observed.5

The exact pathophysiology of obesity in PWS is not fully understood but is likely the result of a combination of hypothalamic dysfunction leading to hyperphagia, dysregulation of hormones controlling hunger and satiety, reduced baseline energy expenditure, and deficiencies in various hormones (e.g., growth hormone, hypogonadism, hypothyroidism).

Obesity affects approximately 40% of children and adolescents with PWS and increases to over 90% in adulthood.6, 7, 8

Previous studies have shown the beneficial effects of an analogue of glucagon-like peptide-1 (GLP1-RA) medications, such as exenatide and liraglutide, in treating type 2 diabetes in PWS. However, there is limited information available on the use of semaglutide in PWS. This study aimed to evaluate the effects of semaglutide on weight loss and glycaemic control in four patients with PWS and type 2 diabetes associated with obesity.