Semaglutide treatment in hypothalamic obesity: Two-Year outcomes on body composition, appetite, and quality of life.

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.