Randomized trial compares adverse event rates in GLP-1/GIP therapy switchers versus continuous users, indicating therapy switching impacts safety.
Introduction and Objective: GLP-1 trials show favorable safety, but less is known about real-world adverse events (AE) rates, particularly among patients who switch therapies. This study examined reported AEs in a cohort of patients with overweight or obesity who switched therapies compared with those on a single treatment. Methods: We analyzed EHR data from GLP-1-naive patients treated for overweight or obesity with semaglutide (Wegovy), tirzepatide (Zepbound), or switching between therapies, randomly sampling 1,500 per group with ≥90 days of enrollment. AEs were captured via required monthly reporting, unprompted app-based logging, or provider messages. AE data through December 30, 2025 were included and compared using chi-square tests with Bonferroni correction. Results: Demographic characteristics were similar across cohorts. Participants who switched treatments consistently reported higher overall and category-specific AE rates (all p <0.001), with the exception of hair loss. Conclusion: AE rates differed across treatment groups, with the lowest tolerability observed among those who switched medications. Further research is needed to better characterize this population, including whether switching is driven by AEs themselves or by other factors such as insurance coverage changes or effectiveness, and to clarify the implications for real-world AE management across treatment groups. Disclosure L. Broffman: Employee; Current; Roman Health Ventures. B.J. Smith: Employee; Current; Roman Health Ventures. L. Aronne: Advisory Panel; Current; Amgen Inc. Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Roche Pharmaceuticals, Eli Lilly and Company, Novo Nordisk, Pfizer Inc. Board Member; Current; Jamieson Wellness Inc. Advisory Panel; Current; Viking Therapeutics, Zealand Pharma A/S, Intellihealth. Stock/Shareholder; Current; Intellihealth, Verdiva. Advisory Panel; Current; Ro. Stock/Shareholder; Current; Skye Bioscience. Board Member; Current; ERX. S. Chai: None. R. Manalac: Employee; Current; Roman Health Ventures. Stock/Shareholder; Current; Eli Lilly and Company, Novo Nordisk, Viking Therapeutics, Altimmune, Roivant, Tempus AI. Funding Roman Health Ventures
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Broffman et al. (2026) studied this question.
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