Real-World Effectiveness of Semaglutide and Tirzepatide Compared With Bariatric Surgery.

OBJECTIVE: Directly compare the real-world effectiveness of semaglutide and tirzepatide to bariatric operations: sleeve gastrectomy and gastric bypass. METHODS: This study included adults with BMI ≥ 35 who received injectable semaglutide or tirzepatide (GLP-1RAs) or sleeve gastrectomy or gastric bypass (bariatric surgery) at two urban health systems from 2018 to 2024. Total weight loss (TWL) was compared up to 3 years post treatment with inverse probability weighting and mixed linear models. Intention-to-treat (any GLP-1RA) and per-protocol (1 year of continuous GLP-1RA orders) analyses were performed. RESULTS: Of 44,025 patients studied, bariatric surgery was associated with greater weight loss at 1, 2, and 3 years post treatment: semaglutide (n = 25,804) TWL (95% CI): 5.4% (5.3%-5.6%), 6.5% (6.4%-6.7%), and 7.4% (7.3%-7.6%); tirzepatide (n = 7308): 9.1% (8.9%-9.4%) and 10.8% (10.2%-11.3%); sleeve gastrectomy (n = 8728): 24.4% (24.3%-24.6%), 22.4% (22.3%-22.5%), and 22.0% (21.8%-22.1%); gastric bypass (n = 2185): 29.8% (29.7%-29.9%), 28.1% (28.0%-28.2%), and 28.4% (28.3%-28.5%). With 1 year of continuous GLP-1RA, findings were: semaglutide TWL: 7.2% (7.0%-7.4%), 8.0% (7.8%-8.2%), and 8.8% (8.6%-9.0%); tirzepatide TWL: 11.7% (11.4%-11.9%) and 11.9% (11.5%-12.3%). CONCLUSIONS: In this retrospective two-center study, bariatric surgery was associated with greater weight loss than GLP-1RAs among patients eligible for both options.