S767 Head-to-Head Comparison of Tirzepatide and Semaglutide: A Dose-Stratified Review of 2 Randomized Controlled Trials

Introduction: Tirzepatide and semaglutide are incretin-based agents with proven weight loss efficacy in type 2 diabetes and obesity. Given their increasing relevance in gastroenterology through effects on metabolic liver disease, gastroesophageal reflux disease, and bariatric management, comparative effectiveness data are needed. We performed a dose-stratified meta-analysis of 2 randomized controlled trials directly comparing tirzepatide and semaglutide. Methods: We identified and extracted data from 2 phase 3 randomized controlled trials: SURPASS-2 (in adults with type 2 diabetes on metformin) and SURMOUNT-5 (in non-diabetic adults with obesity). Tirzepatide (5, 10, or 15 mg weekly) was compared to semaglutide (1.0 mg or 2.4 mg weekly). The primary outcomes were the proportion of patients achieving ≥10% and ≥15% total body weight loss. The secondary outcome was the incidence of adverse gastrointestinal (GI) events. Each tirzepatide dose was compared separately to semaglutide, and risk ratios (RRs) were calculated using a random-effects model. Results: A total of 1,738 participants from 2 trials were included (multiple control arm comparisons). Tirzepatide significantly increased the likelihood of achieving ≥10% weight loss compared to semaglutide (RR = 1.72; 95% confidence interval [CI], 1.22–2.43; P < 0.001). Tirzepatide was also superior for achieving ≥15% weight loss (RR = 3.40; 95% CI, 1.75–6.62; P < 0.001). No significant difference was observed in the incidence of GI adverse events between the 2 agents (RR = 1.06; 95% CI, 0.85–1.31; P = 0.57). Conclusion: In this review of 2 high-quality randomized trials, tirzepatide was significantly more effective than semaglutide for achieving clinically meaningful weight loss, without an increased risk of GI adverse events. These findings highlight tirzepatide as a promising option in obesity management relevant to gastrointestinal care. Additional high-quality studies are required to gain a clearer understanding of their long-term effects.