Semaglutide treatment in hypothalamic obesity: Two-Year outcomes on body composition, appetite, and quality of life
Erlend Gjersdal, Frederik Østergaard Klit, Kåre Schmidt Ettrup, Peter Vestergaard, Eigil Husted Nielsen, Kristian Nilsson Vistisen, Hermann L. Müller, Dorte Melgaard, Jakob Dal
Abstract
PURPOSE: Hypothalamic obesity is a severe complication of craniopharyngioma, marked by hyperphagia and rapid weight gain. Glucagon-like peptide-1 receptor agonists such as semaglutide have shown promising effects on weight reduction, but long-term data on weight outcomes, metabolic parameters and quality-of-life remain limited. METHODS: Four female patients with hypothalamic obesity following craniopharyngioma treatment received semaglutide for 24 months. Assessments included DXA scans, metabolic biomarkers, and The Three-Factor Eating Questionnaire at baseline, 6, 12, and 24 months. Interviews at 24 months explored hunger, side effects and quality of life. RESULTS: After 24 months, median weight loss was 16% (95% CI: 8 to 34%, p = 0.004), with maximal loss of 17% at 6 months. Emotional and uncontrolled eating scores (range: 0-100) decreased by 44 (95% CI: - 69 to - 19, p = 0.011) and 27 units (95% CI: - 63 to 9, p = 0.097), respectively. Interviews revealed reduced hunger, improved self-confidence, less isolation, and higher productivity. Treatment was well tolerated; side effects were mainly mild GI symptoms. Fat and lean mass decreased by 10% (95% CI: 2 to 44%, p = 0.016) and 19% (95% CI: 14 to 26%, p < 0.001), respectively, with stable bone mineral content. Hemoglobin A1c and LDL cholesterol declined by 6.4 mmol/mol (95% CI: 2.3 to 9.9, p = 0.016) and 0.5 mmol/L (95% CI: 0.3 to 0.7, p = 0.012). CONCLUSION: Semaglutide is a safe treatment that led to long-term sustained improvements in eating behavior, weight control, and improved metabolic health. Patients reported an improved quality of life, which persisted after body weight stabilization.