Head-to-head comparison of tirzepatide and semaglutide for weight loss: A systematic review and meta-analysis.

BACKGROUND: Both tirzepatide and semaglutide, once-weekly injectable incretin-based agents, have demonstrated substantial weight-reducing potential in populations with overweight or obesity. However, the relative effectiveness of these two agents remains uncertain. This meta-analysis aimed to directly compare their efficacy in promoting weight loss. METHODS: A systematic search of Europe PMC, Medline, Scopus, and the Cochrane Library was conducted to identify eligible randomized controlled trials (RCTs) and observational studies. Data extraction focused on percentage weight change, absolute weight reduction, and proportions of participants achieving predefined weight loss thresholds (≥5 %, ≥10 %, ≥15 %, and ≥20 %). Pooled analyses were performed using a random-effects model to calculate mean differences (MD) and odds ratios (OR) with 95 % confidence intervals (CI). RESULTS: Twelve studies met the inclusion criteria. Tirzepatide was associated with significantly greater percentage body weight reduction (MD -4.61 %; 95 % CI: -6.03, -3.20; p < 0.00001; I²=95 %) and absolute weight loss (MD -4.76 kg; 95 % CI: -6.09, -3.42; p < 0.00001; I²=87 %) compared with semaglutide. Higher proportions of participants treated with tirzepatide achieved ≥ 5 % (OR 1.52; 95 % CI: 1.03-2.25; p = 0.04; I²=97 %), ≥ 10 % (OR 2.33; 95 % CI: 1.77-3.07; p < 0.00001; I²=95 %), ≥ 15 % (OR 2.82; 95 % CI: 2.06-3.87; p < 0.00001; I²=96 %), and ≥ 20 % (OR 2.28; 95 % CI: 1.62-3.21; p < 0.00001; I²=93 %) weight loss than with semaglutide. CONCLUSIONS: Tirzepatide was associated with numerically greater weight loss across available studies, though high heterogeneity and observational data limit causal inference. These findings suggest tirzepatide may represent a more potent therapeutic option; however, further research is warranted to assess long-term outcomes, cost-effectiveness, and safety across diverse populations.