Original Abstract

AIM: To evaluate the effects of tirzepatide on physical function in adults with overweight or obesity. METHODS: We searched PubMed, Embase, and the Cochrane Library up to July 20, 2025 for randomized controlled trials (RCTs) comparing once-weekly tirzepatide 10 or 15 mg with placebo and reporting validated physical function outcomes. Primary endpoints were changes from baseline in the 36-Item Short Form Health Survey (SF-36) physical function domain and in the Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) physical function subscale. Random-effects models were used to calculate pooled mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed with I2 statistics. RESULTS: Six RCTs comprising 4531 participants, of whom 2802 underwent tirzepatide treatment were included. Tirzepatide significantly improved physical function compared with placebo, both in SF-36 physical function (MD 2.26 points; 95% CI, 1.76-2.76; I2 = 99.8%; p < 0.001) and IWQOL-Lite-CT physical function (MD 10.10 points; 95% CI, 8.61-11.60; I2 = 99.8%; p < 0.001). Subgroup analyses by dose demonstrated consistent benefits for both 10 and 15 mg groups. The overall certainty of evidence, rated by GRADE, was moderate due to risk of bias and inconsistency across studies. CONCLUSIONS: Tirzepatide 10 and 15 mg once weekly significantly improve patient-reported physical function in adults with overweight or obesity. These findings suggest tirzepatide enhances perceived physical capacity and quality of life, although the extremely high between-study heterogeneity limits the interpretability of pooled estimates and warrants cautious interpretation.