1707-P: Association of GLP-1 Use and End-Stage Liver Disease (ESLD) Events in U.S. Adults with Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)

Introduction and Objective: MASLD is a rapidly growing risk factor for ESLD. We evaluated the relationship between GLP-1 use and risk of progression to ESLD among patients with MASLD. Methods: This retrospective cohort study included adult patients with MASLD, evidence of obesity or type 2 diabetes (T2D), and ≥24 months of continuous enrollment in the pre-index period in Optum Market Clarity (12/05/2015-12/31/2024). Patients with other causes of liver disease or severe MASLD complications during the 24-month pre-index period were excluded. Following the pre-index period, initiators of GLP-1 (semaglutide or tirzepatide [any dose]; first fill was the index date) were 1:1 propensity score matched to controls of the same age, sex, metabolic dysfunction-associated steatohepatitis (MASH) status, and indication (obesity and/or T2D) who met the inclusion criteria as of the index date but did not have prior GLP-1 use (i.e. risk set sampling). Time to ESLD (compensated/decompensated cirrhosis, hepatocellular carcinoma, liver transplant, or death) was estimated overall and by indication in Kaplan-Meier and marginal Cox models censoring at dropout or end of data availability. Results: The matched sample included 54,529 patients in each of the GLP-1 and non-GLP-1 cohorts, with 61.3% female, mean (SD) age of 52.3 (11.8) years, and 84.7%, 76.7%, and 61.4% with obesity, T2D, and both, respectively. Mean (median) follow-up was 16.8 (12.9) and 17.2 (14.1) months in the GLP-1 and non-GLP-1 cohort, respectively. In survival analyses, the cumulative incidence of ESLD events for GLP-1 patients was nearly identical to that of non-GLP-1 patients at 6, 12, and 24 months (1%, 3%, and 5%; HR=0.97; p=0.28). Event rates were unchanged in subgroup analyses of patients with obesity, T2D, and both (all p>0.05). Conclusion: Similar ESLD event rates between GLP-1-treated MASLD patients and matched controls may raise questions about the benefit of GLP-1 therapy for MASLD progression and warrant further study. Disclosure D. Nunag: Consultant; Current; Madrigal Pharmaceuticals, Inc. N. Atreja: Employee; Current; Madrigal Pharmaceuticals, Inc. Employee; Ended; Bristol-Myers Squibb Company. C. Parrinello: Employee; Current; Madrigal Pharmaceuticals, Inc. A. Chadha: None. S.E. Clark: Consultant; Current; Madrigal Pharmaceuticals, Inc., Neurocrine Biosciences. M. Davis: Consultant; Current; Madrigal Pharmaceuticals, Inc., AbbVie Inc., Bristol-Myers Squibb Company, Genentech, Inc., Pfizer Inc. B. Thomas: Employee; Current; Madrigal Pharmaceuticals, Inc. F. Lobo: None. A. Martinez: Speaker's Bureau; Current; AbbVie Inc. Consultant; Current; AbbVie Inc., Gilead Sciences, Inc. Speaker's Bureau; Current; Gilead Sciences, Inc. Consultant; Current; Atea, Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Current; Madrigal Pharmaceuticals, Inc., Ipsen Biopharmaceuticals, Inc. Consultant; Current; Ipsen Biopharmaceuticals, Inc. Other - Research, consultant; Current; Cepheid. Speaker's Bureau; Current; Novo Nordisk, Braeburn. Consultant; Current; Altimmune.