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 the...

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Main Authors: Jimmy Wen, Burhaan Syed, Denise Nadora, Christiane How‐Volkman, Ethan Bernstein, Alina Truong, Muzammil Akhtar, Adam Razick, Jose Puglisi, Eldo Frezza
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Endocrinology, Diabetes & Metabolism
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Online Access:https://doi.org/10.1002/edm2.70045
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Summary: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.
ISSN:2398-9238