Efficacy and safety of different doses of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

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Introduction: This study aims to evaluate the effectiveness and safety of different doses of tirzepatide on hypoglycemic, weight-loss, improvement of beta-cell function and insulin resistance in patients with type 2 diabetes mellitus compared with other glucose-lowering drugs or placebo. Research Design and Methods: Searches were conducted for PubMed, Cochrane Library, Web of Science and Embase for randomized controlled trials (RCTs) of tirzepatide from their inception to 2023. The network meta-analysis followed the PRISMA guidelines. Based on the Cochrane risk of bias tool, we analyzed the included RCTs using Stata 15.1. The standardized mean difference and surface under the cumulative ranking curve were presented for each result. An evaluation of publication bias was conducted using funnel plots. Results: Data from 17 studies involving 10405 patients was analyzed. Tirzepatide 10 mg and 15 mg were more effective at hypoglycemic control and weight loss than basal insulin (glargine or degludec) or GLP-1RAs (dulaglutide or semaglutide). Tirzepatide 15mg plays a leading role in lowering body weight (SCURA probability: 98.3%), fasting insulin (95.4%), fasting C-Peptide (91.8%), fasting blood glucose (88.2%) and glycated hemoglobin (85.7%). As for safety, 7407 (72%) had at least one treatment-emergent adverse events and most of that were gastrointestinal adverse events. Conclusions: Tirzepatide 15 mg, not only exhibited a favorable hypoglycemic and weight-loss efficacy, but also achieve a reduction of fasting insulin and fasting C-Peptide by comparison with insulin and GLP1-RAs. It is need of more well-designed RCTs to evaluate potential benefits on insulin resistance and pancreatic beta cell function of tirzepatide.