Tirzepatide Versus Semaglutide for Weight Loss in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Direct Comparative Studies.

This systematic review and meta-analysis compared the weight loss efficacy of tirzepatide versus semaglutide in overweight and obese adults through direct comparative studies. We systematically searched PubMed, Excerpta Medica database (EMBASE), Web of Science, and Cochrane Library databases from inception to April 25, 2025, identifying studies that directly compared tirzepatide and semaglutide for weight management. Inclusion criteria encompassed randomized controlled trials and observational studies reporting percentage change in body weight from baseline. Seven studies totaling 28,980 participants were included, comprising five observational studies and two randomized controlled trials with follow-up durations ranging from six to 12 months. Data analysis was performed using Review Manager 5.4.1 (The Cochrane Collaboration, London, UK) with random-effects models. Results demonstrated that tirzepatide was significantly superior to semaglutide in achieving weight reduction. The pooled analysis showed greater weight loss with tirzepatide compared to semaglutide (standardized mean difference: 0.75, 95% CI: 0.52 to 0.92). At six months, tirzepatide achieved significantly greater weight reduction than semaglutide (mean difference: 1.33, 95% CI: 0.58 to 2.08). Additionally, participants receiving tirzepatide had significantly higher odds of achieving at least 10% weight loss compared to those receiving semaglutide (OR: 0.21, 95% CI: 0.06 to 0.78). High heterogeneity was observed across studies (I² > 90%). This meta-analysis provides evidence that tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, demonstrates superior weight loss efficacy compared to semaglutide in overweight and obese populations. These findings support tirzepatide as a more effective pharmacological option for weight management, though further long-term head-to-head trials are needed to confirm sustained benefits and safety profiles.