Efficacy and safety of tirzepatide, GLP‐1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta‐analysis

Abstract Objective This network meta‐analysis evaluates the efficacy and safety of tirzepatide compared to glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) and other weight loss drugs in the treatment of overweight and obesity. Methods MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP‐1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta‐analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. Results Thirty‐one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight‐related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42–16.34). As compared to placebo, tirzepatide and GLP‐1 RA across all doses had significant increases in gastrointestinal adverse effects. Conclusions The superiority of tirzepatide and GLP‐1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.