Weight Loss Efficacy of Tirzepatide Compared to Placebo or GLP-1 Receptor Agonists in Adults With Obesity or Overweight: A Meta-Analysis of Randomized Controlled Trials With ≥ 20 Weeks Treatment Duration.

Tirzepatide, a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like Peptide 1 (GLP-1) analogue, is a novel medication with comparable pharmacological characteristics and has demonstrated promising weight reduction outcomes in its antidiabetic trials following the approval of liraglutide and semaglutide for long-term weight control. Nonetheless, this efficacy has not been fully explored, so this meta-analysis was aimed to measure the weight loss efficacy and safety of tirzepatide in adults with overweight or obesity. We searched the PubMed, Cochrane, and Embase databases for RCTs of once-weekly tirzepatide vs. placebo or GLP-1 receptor agonists. We included studies involving adult participants who were overweight or obese despite T2DM or OHA use, with a trial duration of at least 20 weeks. The primary outcomes accounted for the mean difference in weight from baseline in the three doses of tirzepatide compared to placebo and GLP-1 receptor agonists, separately. The secondary outcomes included safety profiles and achievement of categorical weight loss of 5%, 10% and 15%. We performed the statistical analysis on RevMan 5.4, GRADE assessment using GRADEpro GDT and the quality of the included studies assessed using the Cochrane risk-of-bias (Version 2) tool. We identified six RCTs in which the data of 6266 subjects were analysed. Once-weekly doses (5, 10 and 15 mg) of tirzepatide were more effective than placebo and GLP-1 RAs. Also, the proportion of patients achieving categorical weight loss goals was higher in the tirzepatide groups than in others. GRADE assessment also indicated high-certainty evidence for ≥ 15% weight loss with tirzepatide and moderate-to-low certainty for lower thresholds. Gastrointestinal side effects appeared similar between the three doses of tirzepatide and GLP-1 RAs, but they were significantly higher than placebo might impact tolerability for certain patients. A dose-dependent tirzepatide was superior to placebo and GLP-1 RAs in weight reduction. However, the lean mass reduction and tolerability require further investigation. ClinicalTrials.gov identifier: NCT04255433.