Comparative efficacy and safety of weekly tirzepatide versus weekly insulin in type 2 diabetes: A network meta‐analysis of randomized clinical trials

Abstract Aim To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once‐weekly formulations such as tirzepatide, a dual glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide receptor agonist, and once‐weekly insulin options such as icodec and basal insulin Fc. Methods A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta‐analysis protocol was registered at OSF registries ( https://osf.io/gd67x ). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes. Results Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15‐mg dose showing the most significant reduction (mean difference [MD] −1.27, 95% confidence interval [CI] −1.49; −1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD −0.70, 95% CI −1.05; −0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15‐mg dose exhibiting the most pronounced effect (MD −12.13, 95% CI −13.98; −10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses. Conclusion Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation.