Comparative Efficacy and Safety of Tirzepatide in Asian and Non-Asian Adults With Obesity Without Diabetes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Tirzepatide, a dual GIP/GLP-1 receptor agonist, produces substantial weight loss in adults with obesity. Given ethnic differences in obesity phenotype and cardiometabolic risk, this systematic review and meta-analysis compared tirzepatide's efficacy and safety between Asian and non-Asian adults without diabetes. METHODS: This PROSPERO-registered review (CRD420261361351) searched PubMed, Scopus, Web of Science and ClinicalTrials.gov through 15 March 2026. Phase 3 SURMOUNT randomised, placebo-controlled trials were classified as Asian (100% Asian participants) or predominantly non-Asian (< 25% Asian participants). The primary outcome was the percentage change in body weight. Secondary outcomes included absolute weight change, body mass index (BMI), waist circumference, weight loss thresholds (≥ 5%, ≥ 10%, ≥ 15%) and adverse events. Random-effects meta-analyses and meta-regression were performed. RESULTS: Five trials (six comparisons; N = 4022) were included: two Asian (SURMOUNT-CN, SURMOUNT-J; n = 148 tirzepatide-treated) and four predominantly non-Asian. Tirzepatide 15 mg/maximum tolerated dose produced an 18.04% greater reduction in body weight versus placebo (95% CI -19.86 to -16.22; p < 0.00001, I = 77%). Percentage weight loss appeared comparable between Asian (-18.16%) and non-Asian (-17.92%) trials (p = 0.94), but this underpowered comparison cannot confirm equivalence. Absolute weight loss was greater in non-Asians (-23.46 vs. -16.72 kg; p = 0.03), largely reflecting higher baseline weight. Safety profiles were similar, with no statistically significant interactions by ethnic subgroup. CONCLUSIONS: Tirzepatide provides clinically meaningful weight reduction, with broadly similar relative percentage efficacy across Asian and non-Asian trial populations. These exploratory, indirect findings do not establish ethnic equivalence and require confirmation in adequately powered, ethnicity-stratified trials. REGISTRATION: The meta-analysis was registered in PROSPERO under the registration number CRD420261361351. The review protocol summary is available on the PROSPERO website.