ESPE Yearbook of Paediatric Endocrinology

Pituitary 27(5) (2024) 723-730.PMID: 39088138

Brief Summary: Patients with hypothalamic pathology often develop hypothalamic obesity (HO), a challenging condition with limited available therapeutic options. This case series reports the effects of semaglutide treatment in HO.

HO is characterized by abnormal weight gain due to hypothalamic pathology, and presents with not only obesity, but also with multiple endocrine alterations, as well as an increased risk of cardiometabolic disorders [11]. HO develops due to dysfunction of the hypothalamus, which may result from either genetic or acquired diseases, or from treatment. Suprasellar tumours are the most common acquired cause of HO [12]. Cases of HO are challenging and have limited treatment options. GLP-1 receptor agonists as a treatment for HO does not appear to depend on a functional leptin–POMC–MC4R pathway, a factor that may prove advantageous in the management of HO [13]. Studies conducted on the effects of exenatide and liraglutide, yet those findings are inconclusive with regard to the consistent weight loss [14-17]. By contrast, semaglutide has been reported to have a more potent effect [18].

This study examined the effect of semaglutide in 4 female patients with HO. Their initial BMI values ranged from 36 to 55.5 kg/m². Following intervention, a reduction in BMI was observed in all cases, with an average decrease of 7.9 BMI (range: 6.7 to 10.1), corresponding to a weight loss of 17.0% (range: 11.3–22.4%). Total body fat and lean mass also decreased. A substantial decrease in body fat was observed in both the trunk (16.4%) and the extremities (upper 21.8%; lower 17.1%). All 4 cases showed improved mobility and physical activity. Unfavorable eating behaviors were reduced after 1 month of treatment, and remained low (emotional eating -41 points, P=0.02, uncontrolled eating -23 points, P=0.11). After 6 months, reductions were observed in HbA1c and total cholesterol.

This study demonstrates that semaglutide is an effective and secure treatment option for HO, with the ability to modify eating behavior, reduce weight, and improve glucose and lipid metabolism.

References: 1. Müller, H.L., et al., Hypothalamic syndrome. Nature reviews Disease primers, 2022. 8(1): p. 24.2. Argente, J., et al., Hypothalamic obesity: from basic mechanisms to clinical perspectives. The Lancet Diabetes & Endocrinology, 2025. 13(1): p. 57–68.3. Iepsen, E.W., et al., Patients with obesity caused by melanocortin-4 receptor mutations can be treated with a glucagon-like peptide-1 receptor agonist. Cell metabolism, 2018. 28(1): p. 23–32. e3.4. Gatta-Cherifi, B., et al., Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial. European Journal of Endocrinology, 2024. 190(4): p. 257–265.5. Roth, C.L., et al., A phase 3 randomized clinical trial using ao nce-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity. Diabetes, Obesity and Metabolism, 2021. 23(2): p. 363–373.6. Zoicas, F., et al., GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. European journal of endocrinology, 2013. 168(5): p. 699–706.7. Lomenick, J.P., M.S. Buchowski, and A.H. Shoemaker, A 52-week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity. Obesity, 2016. 24(6): p. 1222–1225.8. Sciacovelli, C., et al., Semaglutide for treating obesity induced by craniopharyngioma resection: a successful case study. JCEM case reports, 2023. 1(4): p. luad074.