Comparative Efficacy of Tirzepatide vs. Semaglutide in Reducing Body Weight in Humans: A Systematic Review and Meta-Analysis of Clinical Trials and Real-World Data.
This systematic review and meta-analysis compared the weight-loss effectiveness of tirzepatide versus semaglutide in humans by searching PubMed, Scopus, and Web of Science through January 2025. From 751 initial records, seven studies were ultimately included — two randomized controlled trials (RCTs) and five retrospective cohort studies. Using a random-effects model in RStudio, the authors pooled mean differences (MDs) in body weight change between the two agents. The analysis found that tirzepatide was associated with statistically significantly greater weight loss compared to semaglutide (MD = 4.23 kg; 95% CI: 3.22–5.25). Subgroup analyses suggested that higher tirzepatide doses (>10 mg) and longer treatment durations (>6 months) were associated with progressively larger weight differences. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias version 2 tool for RCTs; the authors reported high quality and low risk of bias overall. Publication bias was evaluated via forest plots and Egger's test. Limitations include the small number of included studies (only two RCTs), reliance on retrospective real-world data for most of the analysis, potential heterogeneity across study populations, and the possibility of residual confounding in the observational studies.
Why this grade: Although the meta-analysis pools human data including two RCTs, the small total number of included studies (n=7), the predominance of retrospective observational designs (n=5), and potential heterogeneity across populations limit the overall evidence strength to moderate rather than strong.
Background The aim of the study was to compare the effectiveness of tirzepatide versus semaglutide in producing weight loss. Methods A systematic search was conducted in databases PubMed, Scopus, and Web of Science on January 22, 2025, using search terms ("tirzepatide," "semaglutide," and "weight loss") and their alternatives, which yielded 751 studies in total. After deduplication, title/abstract and full text screening was conducted, and studies were assessed based on the eligibility criteria. After extracting the data, a meta-analysis (MA) was performed through RStudio. Heterogeneity among studies was evaluated with Cochran's Q and I 2 tests. A random-effect model was used to calculate pooled "mean differences" (MDs). Study quality was estimated by Newcastle-Ottawa Quality Assessment Scale (NOS) and Cochrane risk of bias (RoB) version 2 tool, and publication bias was estimated through forest plots and the Egger's test. Results A total of two randomized controlled trials (RCTs) and five retrospective cohorts were included in this MA. MA results showed that compared with the semaglutide, tirzepatide could produce significantly greater weight loss (MD = 4.23; 95% confidence interval (CI): 3.22 - 5.25; P 10 mg dose: MD = 6.50, 95% CI: 5.93 - 7.08, P 6 months duration: MD = 5.00, 95% CI: 3.48 - 6.52, P Conclusion The pooled analysis provides evidence that tirzepatide is better than semaglutide in reducing body weight, regardless of study design. A dose-response relationship exists, and the weight loss magnitude increases with the dose or duration of tirzepatide. The studies that provide this evidence are of high quality and have a low RoB.
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