Efficacy and Safety of Tirzepatide for the Management of Obesity in People With or Without Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Introduction: Obesity affects all level of care. Tirzepatide, a dual Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptor is used for the treatment of type 2 diabetes (T2D), and may have a revolutionary role in the management of obesity. This meta-analysis aims to summarize its outcomes with regards to obesity. Methods: After searching five electronic databases, we retrieved and included relevant randomized controlled trials (RCTs) that assessed the use of tirzepatide for the treatment of T2D and obesity. We calculated risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) with 95% CI for continuous outcomes. Results: Compared to the placebo, there was a greater decrease in mean body weight for tirzepatide at all doses, the greatest with 10 mg (SMD -3.36 kg; CI 95% -4.57 to -2.15). Tirzepatide showed a higher incidence of weight reduction of ≥ 15% at all doses, the highest being at 15mg (RR 15.25; CI 95% 5.04 to 46.13). Compared to insulin, the change in mean body weight was greater for tirzepatide at all doses, the highest at 15 mg (SMD -2.13; CI 95% -2.38 to -0.189). Tirzepatide showed a higher incidence of weight reduction of ≥ 15% at all doses, the highest being at 15 mg dosage (RR 82.42; CI 95% 35.45 to 191.62). Compared to monotherapy with GLP-1 receptor agonist (RA), the change in mean body weight was greater for tirzepatide at all doses, the highest at 15 mg (SMD -3.97kg; CI 95% -5.75 to -2.29). Tirzepatide was associated with a higher incidence of weight reduction of ≥ 15% at all doses, the highest at 15 mg (RR 13.23; CI 95% 2.43 to 71.93) Figure 1. Conclusion: In this meta-analysis investigating the effects of tirzepatide on unhealthy weight in patients with obesity, with or without T2D, we were able to demonstrate greater weight loss effects compared to patients on placebo, basal insulin, or single (GLP-1) agonists. Pharmacotherapy for obesity with tirzepatide should be offered within a multidisciplinary specialist service and as an adjunct to a balanced lifestyle and increased physical activity.Figure 1.: Comparison of mean change in body weight between patients receiving Tirzepatide or placebo. IV, inverse variance.