Comparing Efficacy and Safety of Different Doses of Tirzepatide for the Treatment of Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Our study assessed the efficacy and safety of the three primary tirzepatide (TZP) doses, 5 mg, 10 mg, and 15 mg using network meta-analysis to assess their relative impact on type 2 diabetes mellitus (T2DM) treatment. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Two authors independently screened online databases, including PubMed, Cochrane Library, and Embase. We employed the keywords "Type 2 diabetes OR T2DM or diabetes" AND "Tirzepatide OR LY3298176 OR twincretin OR dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist" AND "randomized controlled trial". The outcomes evaluated in this study comprised changes in hemoglobin (Hb)A1c levels from baseline (%), changes in weight from baseline (Kg), changes in fasting serum glucose from baseline (mg/dL), and occurrences of serious adverse events (SAE), adverse events (AE) and major adverse cardiovascular events (MACE). A total of eight studies met the inclusion criteria and were included in this meta-analysis. Our findings suggest that among the evaluated doses, TZP at 15 mg demonstrated superior effectiveness in reducing HbA1c, weight, and fasting serum glucose compared to doses of 10 mg and 5 mg. Notably, the reduction in HbA1c and weight showed a dose-dependent trend, with the 15 mg dose achieving the most substantial benefits. The safety analysis indicated that while serious adverse events and major adverse cardiovascular events (MACE) did not significantly differ among the three doses, the risk of overall adverse events was notably higher in the 10 mg and 15 mg TZP groups compared to the 5 mg group.