2324-P: GLP-1RA Discontinuation in People with Obesity: Real-World Insights across Disease Burden Subgroups

Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity, yet real-world discontinuation patterns remain poorly characterized, particularly among individuals with cardiometabolic comorbidities. This study used contemporary real-world data to evaluate discontinuation across disease burden subgroups and to explore treatment persistence outside of clinical trials. Methods: We conducted a cohort study using Truveta data from the United States, including adults with obesity initiating semaglutide, tirzepatide, or liraglutide between 2021-2025. Discontinuation was defined as a ≥60-day gap in supply. Results were analyzed by four groups: 1) Obesity (overall), 2) Obesity + Type 2 Diabetes (T2D), 3) Obesity + T2D + cardiovascular disease (CVD), 4) Obesity + T2D + Metabolic dysfunction-associated steatotic liver disease (MASLD). Kaplan-Meier methods were used to estimate the cumulative probability of discontinuation. Results: The cohort included 201,391 new users (median age 53 years; 51% aged 45-64 years, 68% female). Disease burden was high: 46% had T2D, 23% T2D + CVD, 5% T2D + MASLD. At index, semaglutide (68%) was the most frequently dispensed in the overall obesity cohort, followed by tirzepatide (26%), a pattern consistent across disease burden subgroups. Cumulative probability of discontinuation at 12-months was 55% (Group 1; 57% semaglutide, 43% tirzepatide), 49% (Group 2), 51% (Group 3), and 47% (Group 4). Median treatment duration was greater in multimorbid groups: 68 days longer in Group 4 than Group 1. Conclusion: Real-world GLP-1RA discontinuation is common in people with obesity, yet individuals with greater cardiometabolic disease burden appear to remain on therapy longer, highlighting the need to support persistence in lower-risk groups. Further analyses of switching, reinitiation, reasons for discontinuation, and potential differences between agents may identify opportunities to promote sustained obesity treatment and individualized care. Disclosure J. Almandoz: Consultant; Current; AbbVie Inc., Amgen Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kailera, Novo Nordisk, Metsera, Rhythm Pharmaceuticals, Inc., Rivus. S. Saydam: Employee; Current; Boehringer Ingelheim International GmbH. C. Sartini: Employee; Current; Boehringer Ingelheim International GmbH. S. Eng: Employee; Current; Truveta Inc. C. Howe: Employee; Current; Truveta Inc. N. Tabatabaeepour: Employee; Current; Truveta Inc. J.M. Schattenberg: Consultant; Current; 89bio, Inc., Akero Therapeutics, Inc., Alentis Therapeutics, Alexion Pharmaceuticals, Inc., Altimmune, AstraZeneca, Bionorica, Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., HistoIndex, Ipsen Biopharmaceuticals, Inc., Inventiva Pharma, Kriya Therapeutics, Madrigal Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Pfizer Inc., Roche Pharmaceuticals, Sanofi, Siemens. Speaker's Bureau; Current; AbbVie Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Ipsen Biopharmaceuticals, Inc., Lilly, Madrigal Pharmaceuticals, Inc., Novo Nordisk. Stock/Shareholder; Current; Hepta Bio. Funding Boehringer Ingelheim