Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide.
This retrospective cohort study used electronic health records from a large health system in Ohio and Florida (January 2021–June 2025) to examine real-world obesity treatment patterns and weight changes among adults who discontinued injectable semaglutide or tirzepatide within 3–12 months of initiation. A total of 7,938 patients (mean age ~56 years; ~64% female) were included. The study found that within one year of discontinuation, roughly 19.6% restarted the same medication and 35.2% received an alternative obesity treatment (most commonly another medication). Patients treated for obesity lost a mean of 8.4% of body weight before discontinuation, while those treated for type 2 diabetes lost 4.4%. In the year following discontinuation, the average weight change was modest (+0.5% for obesity indication; −1.3% for T2D indication), but with considerable individual-level variability—meaning some patients regained weight substantially while others did not. Key limitations include the retrospective, observational design (precluding causal inference), potential confounding by unmeasured factors, and restriction to a single health system in two U.S. states, which may limit generalizability.
Why this grade: Large real-world human cohort (n=7,938) provides meaningful observational evidence, but the retrospective design and lack of randomization or a control group limit causal conclusions.
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.
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