Hendra Zufry, Timotius Ivan Hariyanto
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. © 2026 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Division of Endocrinology, Metabolism, and Diabetes, Thyroid Center, Department of Internal Medicine, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Division of Endocrinology, Metabolism, and Diabetes, Thyroid Center, Department of Internal Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia; Innovation and Research Center of Endocrinology, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Microbiology, Faculty of Medicine, Universitas Airlangga, Jawa Timur, Surabaya, Indonesia; Department of Microbiology, Dr. Soetomo General Academic Hospital, Jawa Timur, Surabaya, Indonesia
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