Effectiveness and safety of GLP-1 receptor agonists in craniopharyngioma patients with obesity: A multicentre real-world study.

AIMS: Acquired hypothalamic obesity (aHO) following craniopharyngioma (CP) is a challenging condition with limited therapeutic options. This study aimed to assess the real-world effectiveness and safety of GLP-1 RAs in this population. MATERIALS AND METHODS: CranioGLP1 is a retrospective multicentre study including 116 adults with aHO treated with one or more GLP-1 RAs across 16 French obesity centres. Demographic, clinical, and therapeutic data were collected from medical records. Weight outcomes, adverse events, and predictors of response were analysed. RESULTS: Patients had a mean age of 44.4 ± 13.5 years and a mean BMI of 40.1 ± 8.6 kg/m, 42% had type 2 diabetes. Over a mean follow-up of 44 months, mean weight loss was -4.6% (±12.5), with high interindividual variability; 51% achieved ≥5% weight loss, and 28% ≥10%. Semaglutide (mean dose 1.2 mg/week) was associated with the greatest reduction (-6.8%), particularly in patients without diabetes (-8.5% ± 12.3 vs. -3.9% ± 10.0 in those with diabetes; p = 0.032). Endocrine adverse events occurred in 12% and 10% of patients with adrenal or vasopressin deficiency decompensation, respectively, with 8% requiring hospitalisation. Gastrointestinal intolerance led to treatment discontinuation in 13% of cases. CONCLUSIONS: GLP-1 RAs at submaximal doses induce moderate, yet clinically meaningful weight loss in adults with aHO, with semaglutide showing the highest efficacy. Given the non-negligible risk of hormonal decompensation, specific endocrine monitoring is essential.