Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.

Aims: To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. Materials and methods: Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. Results: From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. Conclusion: This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.