Who Wins the Battle Against Obesity? A Network Meta‐Analysis Comparing Tirzepatide and Semaglutide

ABSTRACT Introduction Pharmacological therapies are recommended for individuals with obesity. Semaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1), and tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and GLP‐1 receptor agonist (GIP/GLP‐1), are among the leading pharmacological options for obesity treatment. This network meta‐analysis (NMA) aims to evaluate the comparative efficacy of these two agents in reducing body weight and improving glycemic parameters. Methods Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively). Results A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years. Tirzepatide demonstrated superiority over semaglutide in percentage weight reduction (mean difference MD 6.10%; 95% CI: 3.64, 8.57), absolute weight loss (MD 4.55 kg; 95% CI: 1.28, 7.83), BMI reduction (MD 1.71 kg/m 2 ; 95% CI: 0.08, 3.34), and waist circumference reduction (MD 2.89 cm; 95% CI: 1.25, 4.53). Regarding glycemic parameters, tirzepatide was also more effective than semaglutide in reducing HbA1c (MD 0.33%; 95% CI: 0.20, 0.46) and fasting blood glucose (MD 10.39 mg/dL; 95% CI: 4.48, 16.29). Conclusion In this NMA, tirzepatide appeared to be superior to semaglutide in both body weight reduction and improvement of glycemic indices.