1709-P: Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists Compared with Leptin in a Retrospective Study of Patients with Partial Lipodystrophy

Introduction and Objective: Lipodystrophy (LD) syndromes are a group of rare disorders of abnormal fat distribution and severe metabolic disease. The only approved therapy for LD is recombinant leptin, which is approved for generalized but not partial forms of LD. Recently it has been shown that glucagon-like peptide 1 receptor agonist (GLP1RA) therapies, such as semaglutide and tirzepatide, may be effective in treating health complications of LD. It is unknown how efficacy of GLP1RA therapies compares to leptin therapy in patients with LD. Methods: Retrospective analysis of patients with partial lipodystrophy who were initially treated with leptin before switching to either semaglutide or tirzepatide, or were on both leptin and GLP1RA concurrently, and who were tracked in the context of an ongoing natural history study. Results: Eleven patients with partial LD (aged 16-85 years, 100% females) were initially treated with leptin (mean duration 104 ± 38 months) before switching to GLP1RA based therapy (either semaglutide or tirzepatide, mean duration 32 ± 13 months). There was a significant reduction in HbA1c during GLP1RA compared to prior leptin therapy (mean difference -1.1%, range 0.1% to -4.75%, p=0.001). Other metabolic parameters including BMI, triglycerides, and liver stiffness and liver steatosis were unchanged. Conclusion: In patients with partial LD, GLP1RA may lead to better diabetes control compared to leptin, with comparable control of other metabolic parameters. Disclosure B. Podyma: None. M. Lightbourne: None. R.J. Brown: Research Support; Current; Regeneron Pharmaceuticals Inc., Marea, Pfizer Inc., Chiesi USA, Inc. Funding Supported by the NIH intramural research program