Endocrine Abstracts

Background: Hypothalamic obesity (HO) is defined as rapid weight gain, hyperphagia and lack of satiety due to physical hypothalamic destruction. HO does not usually respond to lifestyle modification and no pharmacotherapies are specifically approved for treating HO. Efficacy of glucagon-like peptide-1 (GLP-1) agonists, which suppress appetite via hypothalamic satiety centres, is uncertain in HO.

Case series: We commenced seven patients (3 female; aged 13–19 years) with HO secondary to suprasellar tumours (3 craniopharyngioma, 3 germinoma, 1 Rathke‘s cyst) on GLP-1 agonists (liraglutide or semaglutide). At treatment initiation, mean BMI was 37.4 kg/m² (±3.0) with mean BMI-SDS 3.38 (±0.3). Complications of excess weight included 2/6 with obstructive sleep apnoea requiring overnight ventilation, 1/6 with type 2 diabetes mellitus and 1/6 with non-alcoholic fatty liver disease.

Case 1 commenced on liraglutide (3 mg daily) aged 13.4 years and lost 3.2% bodyweight (BMI–SDS reduction 0.14) after 3 months, which continued at 6 months (8.3% weight loss; 0.44 BMI SDS-reduction) and 12 months (11.8% weight loss; −0.63 BMI–SDS reduction).

Case 2 commenced on liraglutide (3 mg daily) aged 16.2 years and lost 4.1% bodyweight (BMI–SDS reduction 0.24) after 3 months, which continued at 6 months (7.0% weight loss; 0.41 BMI SDS-reduction) and 12 months (8.6% weight loss; 0.63 BMI–SDS reduction).

Case 3 commenced on semaglutide (2 mg weekly) aged 13.8 years, after continued weight gain on liraglutide, and weight stabilised with 0.61% weight gain (0.32 BMI–SDS reduction) over 12 months.

Case 4 commenced semaglutide (1 mg weekly) aged 18.9 years, lost 2.79% bodyweight (BMI–SDS reduction 0.18) after 3 months and 1.86% weight loss (0.18 BMI SDS-reduction) at 6 months.

Encouraged by these results, three further patients recently commenced semaglutide therapy but auxological follow-up data is awaited, including one patient who was unsuccessfully established on liraglutide therapy due to nausea. All six patients reported increased satiety and less pre-occupation with food.

Conclusion: Our initial results demonstrating response to GLP-1 therapy in HO are promising. More longer-term data are required to evaluate its use for treating HO and associated sequelae. Weight stabilisation, rather than loss, may also be considered to reflect a successful treatment outcome in this challenging patient cohort.