Semaglutide for Treating Paediatric Craniopharyngioma‐Related Obesity: A Multicentre Case Series

ABSTRACT Aims Obesity is a complication of childhood craniopharyngioma that remains difficult to treat. We investigated whether semaglutide was associated with a decrease in BMI among adolescents with craniopharyngioma‐related obesity. Material and Methods This multicentre retrospective study included 20 patients < 18 years old with craniopharyngioma and obesity (BMI > 2 WHO Z ‐score) from 2019 to 2024 (source population: 139 children with craniopharyngioma, including 36 children with obesity). They received off‐label semaglutide with dose titration (0.25–2 mg/week), tailored to tolerance and clinical response. The primary outcome was the within‐patient comparison of BMI change from −12 months to treatment initiation and from initiation to +12 months. Results At semaglutide initiation, patients were 14.0 ± 3.9 years old, the interval since craniopharyngioma diagnosis was 6.3 ± 4.7 years, and BMI was 33.4 ± 3.9 kg/m 2 (3.2 ± 0.7 Z ‐score). Tumour treatment was surgery alone (8/20), surgery and proton therapy (11/20), or proton therapy alone (1/20). All patients had growth hormone and TSH deficiency; 19/20 had ACTH and AVP deficiency. In the year before treatment, patients gained 3.5 ± 4.4 kg/m 2 in BMI and 0.6 ± 1.6 in BMI Z ‐score; after 1 year of semaglutide therapy, they lost 2.5 ± 3.9 kg/m 2 in BMI and 0.5 ± 0.5 in BMI Z ‐score (paired comparisons, p < 0.001 and p = 0.004, respectively). During treatment, BMI decreased by 10% or more in 40% of patients (95% CI: 19%–64%). Gastrointestinal side effects occurred in 30% of patients but were mild. No cases of treatment discontinuation, pituitary insufficiency decompensation or tumour recurrence were observed. Conclusions Semaglutide was associated with reversal of weight gain among adolescents with craniopharyngioma‐related obesity.