Network meta-analysis of cardiovascular outcomes in randomised controlled trials of new antidiabetic drugs.

Abstract

Purpose: Few randomised controlled trials directly compared the effect of new antidiabetic drugs on cardiovascular outcomes in patients with type 2 diabetes (T2D). We performed a network meta-analysis to assess the cardiovascular effects of these drugs. Methods: We searched for randomised controlled trials that reported rates of major adverse cardiovascular events (MACE) and deaths in T2D patients with established cardiovascular risks, involving glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose co-transporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Data were analysed using frequentist approach and Bayesian framework in R. Results: Seven randomised controlled trials with altogether 62268 T2D patients were included for analysis. Compared to placebo, GLP-1 RAs and the SGLT-2 inhibitor reduced MACE (OR 0.89, 95%CI 0.82-0.97 and OR 0.85, 95%CI 0.73-0.99, respectively) and all-cause mortality (OR 0.89, 95%CI 0.80-0.99 and OR 0.67, 95%CI 0.55-0.81, respectively). The SGLT-2 inhibitor was more beneficial than GLP-1 RAs in reducing all-cause mortality (OR 0.76, 95%CI 0.61-0.94). DPP-4 inhibitors increased all-cause mortality when compared to GLP-1 RAs (OR 1.16, 95%CI 1.01-1.33) and the SGLT-2 inhibitor (OR 1.53, 95%CI 1.24-1.89). Conclusions: GLP-1 RAs and the SGLT-2 inhibitor reduced the risk of MACE and all-cause mortality. DPP-4 inhibitors were inferior to these two drug classes in reducing cardiovascular events. The SGLT-2 inhibitor was the best in preventing deaths among the three antidiabetic drugs classes.