Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials.

Background: Tirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not been investigated.

Aim: This meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obese patients without diabetes.

Method: PubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively.

Results: Three RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02), BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18), WC (SMD - 0.91, 95% CI - 1.14 to - 0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo.

Conclusion: Tirzepatide significantly reduced weight and improved metabolic markers among overweight or obese without diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.