GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases

Background: Patients with hypothalamic pathology often develop morbid obesity, causing severe metabolic alterations resulting in increased morbidity and mortality. Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic patients and cause weight loss in obese patients by yet unknown mechanisms. Here we tested whether GLP-1 analogues were also effective in the treatment of obesity and associated metabolic alterations in patients with hypothalamic disease. Methods: Nine patients (eight with type 2 diabetes mellitus) with moderate to severe hypothalamic obesity were treated with GLP-1 analogues for up to 51 months. Body weight, homeostasis model assessment - insulin resistance (HOMA-IR), HbA1c and lipids were assessed. Results: Eight patients experienced substantial weight loss (-13.1 +/- 5.1 kg (range -9 to -22)). Insulin resistance (HOMA-IR -3.2 +/- 3.5 (range -9.1 to 0.8)) and HbA1c values (-1.3 +/- 1.4% (range -4.5 to 0.0)) improved under treatment (24.3 +/- 18.9 months (range 6 to 51)). Five patients reported increased satiation in response to the treatment. Two of the eight patients complained about nausea and vomiting and one of them abandoned therapy because of sustained gastrointestinal discomfort after 6 months. One patient suffered from intolerable nausea and vomiting and discontinued treatment within 2 weeks. Conclusion: GLP-1 analogues can cause substantial and sustained weight loss in obese patients with hypothalamic disease. This offers a new approach for medical treatment of moderate to severe hypothalamic obesity and associated metabolic alterations. European Journal of Endocrinology 168 699-706