Comparative Efficacy of Tirzepatide Versus GLP-1 Receptor Agonists on Glycaemic Control and Body Weight in Adults With Type 2 Diabetes: A Systematic Review and Meta-Analysis of Head-to-Head Randomised Controlled Trials

Abstract Purpose Dual incretin receptor agonists targeting GIP and GLP-1 receptors represent a novel therapeutic approach for the management of type 2 diabetes mellitus. Tirzepatide, the first agent in this class, has demonstrated substantial metabolic benefits compared with selective GLP-1 receptor agonists. This study aimed to compare the efficacy of tirzepatide versus single GLP-1 receptor agonists on HbA1c and body weight in adults with T2DM. Methods A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines to compare tirzepatide with GLP-1 RAs in adults with T2DM. Randomised controlled trials with a minimum duration of 24 weeks were included. Outcomes were changes in HbA1c (%)and body weight (kg). Random-effects meta-analyses were performed with dose-stratified subgroup analyses for tirzepatide 5 mg, 10 mg, and 15 mg. Results Five randomised controlled trials were included. Compared with GLP-1 RAs, tirzepatide achieved greater reductions in HbA1c across all doses, with pooled mean differences ranging from − 0.89% to − 0.95%. Individual trials demonstrated greater HbA1c reductions with increasing tirzepatide dose. Body-weight reduction showed a clear dose-sensitive response, with pooled mean differences of − 6.2 kg at 5 mg, − 8.6 kg at 10 mg, and − 10.7 kg at 15 mg versus GLP-1 RAs. Conclusion In adults with T2DM, tirzepatide provides superior glycaemic and weight-loss efficacy compared with GLP-1 receptor agonists. While both outcomes demonstrate dose-responsive effects, body-weight reduction shows greater sensitivity to dose escalation, supporting dose-tailored treatment strategies.