Retrospective EHR study from a large Ohio and Florida health system tracking obesity treatments and weight trajectories after semaglutide or tirzepatide discontinuation (January 2021–June 2025). Characterizes what treatments patients transition to post-discontinuation and quantifies weight regain patterns by reason for stopping (adverse events, cost, access, patient preference). Provides real-world data on the clinical management of GLP-1 RA discontinuation—essential for understanding the treatment landscape when first-line pharmacotherapy must be stopped.
Abstract
AIMS: To describe obesity treatments in real-world settings after discontinuation of semaglutide or tirzepatide and variability in weight change post-discontinuation.
MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2021, to 30 June 2025, in a large health system in Ohio and Florida. Adults with overweight or obesity who initiated injectable semaglutide or tirzepatide for obesity or T2D between 2021 and 2023 and discontinued the medication within 3-12 months were included. Main outcomes were reinitiation of the index medication or receipt of an alternative treatment, body weight changes from baseline to index medication discontinuation and from discontinuation to 1-year post discontinuation.
RESULTS: A total of 7938 patients (mean [SD] age, 55.7 [13.4] years; 5061 [63.8%] female) were identified. During 1-year post-discontinuation, 19.6% restarted the index medication and 35.2% received an alternative obesity treatment, including starting another medication (27.4%), lifestyle modification visit (13.7%) and metabolic and bariatric surgery (0.6%). Mean percentage weight change from baseline to discontinuation was -8.4% [95% CI, -8.7%, -8.1%] when treating obesity and -4.4% [95% CI, -4.7%, -4.2%] when treating T2D. Mean percentage weight change from discontinuation to 1 year later was 0.5% [95% CI, 0.0%, 1.0%] when treating obesity and -1.3% [95% CI, -1.6%, -1.0%] when treating T2D; however, there was considerable individual-level variability.
CONCLUSION: In this large sample of patients who discontinued semaglutide or tirzepatide, reinitiation of the original medication or receipt of alternative obesity treatment was common. The average weight change 1-year post-discontinuation was relatively small; however, there was considerable individual-level variability.
Authors
Gasoyan, Hamlet; Schulte, Rebecca; Boyer, Christopher B; Casacchia, Nicholas J; Butsch, W Scott; Le, Phuc; Aminian, Ali; Griebeler, Marcio L; Burguera, Bartolome; Rothberg, Michael B