MON-729 - Real-World Prescribing Patterns of Combined Metreleptin and GLP-1 Receptor Agonist Therapy in Adults with Lipodystrophy

Background: Metreleptin is a key therapy for patients with severe lipodystrophy syndromes that improves metabolic dysfunction by correcting underlying leptin deficiency. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) ameliorate dysglycemia and hypertriglyceridemia in patients with type 2 diabetes and, more recently, have shown metabolic benefit in lipodystrophy. Preclinical data suggest central nervous system crosstalk and potential synergy between leptin and GLP-1 signaling. In addition, recent case reports describe metabolic improvement following addition of GLP-1RA therapy to ongoing metreleptin therapy in patients with lipodystrophy, raising the possibility that combined therapy may represent an attractive strategy in clinical practice.

Methods: Using Komodo Healthcare claims data from 2016 through 2025, we conducted a descriptive real-world analysis of sustained GLP-1RA therapy initiated on a background of ongoing metreleptin therapy among adults aged ≥20 years with lipodystrophy ( ≥4 claims for each medication). The index date was defined as the last observed metreleptin claim for the metreleptin monotherapy group, and the last observed metreleptin claim prior to GLP-1RA initiation for the combination metreleptin/GLP-1RA therapy group to reflect a comparable stage of treatment. Metabolic comorbidities were identified using diagnosis codes. Fisher exact tests were used to compare proportions between groups (P < 0.05).

Results: Among 125 adults with lipodystrophy receiving sustained metreleptin therapy, 22 (18%) subsequently initiated sustained add-on GLP-1RA therapy. Patients receiving combination metreleptin/GLP-1RA therapy were older, with a higher proportion aged ≥50 years compared to those on metreleptin monotherapy (45% vs. 22%, P=0.03). Sex distribution was similar between groups (82% vs. 85% female). The prevalence of diabetes (95% vs. 80%), dyslipidemia (91% vs. 83%), metabolic dysfunction-associated steatotic liver disease (59% vs. 51%), cardiovascular disease (36% vs. 34%), and history of pancreatitis (32% vs. 38%) was comparable between combination metreleptin/GLP-1RA therapy and metreleptin monotherapy groups.

Conclusions: GLP-1RA therapy is used in combination with metreleptin in a substantial subset of patients with lipodystrophy in clinical practice. Patients receiving combination therapy had a high burden of metabolic comorbidities prior to GLP-1RA initiation, comparable to those receiving metreleptin alone. These real-world prescribing patterns highlight the need for prospective studies to evaluate the safety and efficacy of combination metreleptin/GLP-1RA therapy in patients with lipodystrophy.

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