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

Abstract

Background: The prevalence of cardiovascular disease is high in patients with type 2 diabetes mellitus (T2DM). However, evidence from randomised controlled trials (RCTs) that directly compared the effect of new antidiabetic drugs on cardiovascular outcomes in these patients was limited. We performed a network meta-analysis to assess the cardiovascular safety of different classes of these drugs. Methods: We searched for RCTs 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 in T2DM patients with established cardiovascular risks. RCTs that reported rates of major adverse cardiovascular events and mortality were eligible to be included. Both frequentist approach and Bayesian framework were used for analysis in R. Results: We included 7 RCTs with altogether 62268 T2DM patients in our network meta-analysis. GLP-1 RAs and the SGLT-2 inhibitor reduced MACE (OR 0.89, 0.82-0.97 and 0.85, 95%CI 0.73-0.99, respectively) and all-cause mortality (0.89, 0.80-0.99 and 0.67, 0.55-0.81, respectively) when compared to placebo. The SGLT-2 inhibitor reduced all-cause mortality more than GLP-1 RAs (OR 0.76, 95%CI 0.61-0.94). Moreover, DPP-4 inhibitors were comparable to placebo but associated with increased allcause mortality when compared to the SGLT-2 inhibitor (1.53, 1.24-1.89) and GLP-1 RAs (1.16, 1.01-1.33), respectively. Conclusions: The SGLT-2 inhibitor and GLP-1 RAs reduced all-cause mortality and MACE, which were both superior to DPP-4 inhibitors. The SGLT-2 inhibitor was more beneficial in preventing deaths than the other two drugs classes, which can be used as the prior secondline treatment for T2DM patients to reduce cardiovascular risks.