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Meta-Analysis
. 2025 May;8(3):e70045.
doi: 10.1002/edm2.70045.

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

Jimmy Wen  1 , Burhaan Syed  1 , Denise Nadora  1 , Christiane How-Volkman  1 , Ethan Bernstein  1 , Alina Truong  1 , Muzammil Akhtar  1 , Adam Razick  2 , Jose Puglisi  1 , Eldo Frezza  1
Affiliations
Meta-Analysis

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

Jimmy Wen et al. Endocrinol Diabetes Metab. 2025 May.

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.

Keywords: diabetes; meta‐analysis; semaglutide; tirzepatide; weight loss.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA diagram of article selection process.
FIGURE 2
FIGURE 2
Estimated treatment differences in weight loss between tirzepatide and semaglutide.
See this image and copyright information in PMC

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