Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Semaglutide and Tirzepatide: A Nationwide Multicenter Study

Introduction: Real-world data directly comparing the safety, tolerability, and effectiveness of semaglutide and tirzepatide in patients with obesity remain limited. This nationwide multicenter observational study compared short-term adverse events, treatment discontinuation, body weight loss (BWL), and metabolic outcomes between the two treatments. Methods: This study included 2, 549 patients with obesity treated with semaglutide (n = 1, 434) or tirzepatide (n = 1, 115). Adverse events, including time to onset, dose at occurrence, and related discontinuation, were evaluated. Changes in BWL and metabolic parameters up to 6 months were assessed. Subgroup analyses were performed in patients with and without type 2 diabetes mellitus (T2DM). Results: At least one adverse event occurred in 50.9% in the semaglutide group and 51.0% in the tirzepatide group (p = 0.524), with gastrointestinal events the most frequently reported. Overall adverse event rates were comparable between groups; however, musculoskeletal and allergic reactions were more common in the tirzepatide group. The onset of gastrointestinal, neuropsychiatric, musculoskeletal symptoms, and hypoglycemia occurred earlier in the tirzepatide group. Discontinuation due to adverse events was similar between groups, except for pancreatic events, which were more frequent in the semaglutide group (p = 0.006). Tirzepatide was associated with greater early BWL at all time points. At 6 months, median percentage BWL was 12.6% with semaglutide and 14.4% with tirzepatide. HbA1c reductions were comparable between groups in patients with T2DM. Conclusion: In real-world clinical practice, semaglutide and tirzepatide show similar short-term tolerability and treatment persistence, although tirzepatide is associated with a higher incidence of musculoskeletal and allergic reactions and greater early BWL.