Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies

Abstract

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an efficacious treatment for type 2 diabetes mellitus (T2DM) and have demonstrated substantial weight loss effects. This systematic review compares two prevalent GLP-1RAs, tirzepatide and semaglutide, with their weight loss effects and rates of adverse events (AEs). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase and Cochrane Library for direct comparative studies between tirzepatide and semaglutide. A meta-analysis was conducted via a random-effects model to analyse the differences in weight loss outcomes between study cohorts. Results: Four studies, with 28,827 patients (14,870 tirzepatide/13,928 semaglutide), mean age of 55.7 years (52.0 to 63.7) and mean follow-up of 35.9 weeks (23.6 to 44.6), were included in this study. Mean weight change across four studies for tirzepatide and semaglutide was −11.4% (−15.3% to −8.27%) and −7.3% (−8.3% to −6.08%), respectively. The meta-analysis supports these findings with a mean difference of −4.84 kg (95% CI: −6.21 to −3.47), favouring tirzepatide. The most common AEs were minor and moderate-severity gastrointestinal (GI) AEs. Conclusion: Current literature supports tirzepatide demonstrating a higher impact on weight loss than semaglutide, with both demonstrating high rates of minimal- to moderate-severity AEs. Further research with comparative head-to-head trials will better elucidate these weight loss effects and safety profiles.