Endocrine Abstracts

JOINT868

Background: Hypothalamic obesity (HO) is a complex disorder marked by rapid and excessive weight gain, following damage to key hypothalamic structures responsible for energy homeostasis and appetite. Traditional lifestyle intervention often fails to result in meaningful or sustained reduction in body mass index (BMI) for general obesity, and are even less efficacious with HO. Favourable outcomes have been reported with GLP-1 agonist semaglutide for obesity which suggest it could be beneficial for adolescents with HO.

Method: Prospective observational study of the off-label use of semaglutide in adolescents with acquired HO across two tertiary paediatric hospitals, according to a standardised treatment and monitoring protocol. Dose titrated to effect (appetite suppression and sustained weight loss without significant adverse effects) starting at 0.25mg/week with four weekly increases up to a maximum of 2mg/week by 16 weeks at the earliest if clinically indicated. We report efficacy, tolerability, safety, impact on quality of life (QOL) and eating behaviours.

Results: Ten adolescents (60% male, age 11.6-17.3 years) with acquired HO are receiving semaglutide plus lifestyle intervention. Primary diagnoses include craniopharyngioma (n = 6), pituitary adenoma (n = 2), pineal tumour (n = 1) and bilateral thalamic infarcts (n = 1). After 8 weeks of therapy, 9/10 participants had a reduction in BMI SDS (range 0.03 to 0.18 SD) and BMI expressed as a percentage of 95th percentile (range 2 to 35%). Five participants have completed 24 weeks of therapy thus far with 4/5 participants experiencing a reduction in BMI SDS (range 0.03 to 0.18 SD) and BMI expressed as a percentage of 95^th percentile (range 1 to 13%). Two patients have achieved at least a 5% reduction in total body weight. Waist to height ratio has reduced in all cases (mean reduction 5.0%, range 1.5 to 9.8%). 24-week data for the remaining 5 participants is awaited. Appetite suppression was evident from the starting dose with gastrointestinal side effects (vomiting, nausea and loose stool) being the most common, primarily occurring at treatment initiation or following dose escalation. No serious adverse events or therapy discontinuation has occurred. Treatment was associated with increased satiety responsiveness and slower eating measured by the Child Eating Behaviour Checklist. QOL assessments identified baseline deficits in physical comfort and body esteem, which have demonstrated the greatest improvements following treatment.

Discussion: Semaglutide is a promising therapy for HO. Data suggests this is a safe and effective treatment, although individual responses have varied. Further evaluation of long-term efficacy and safety is required.