Cardiovascular outcomes in trials of new antidiabetic drug classes

Abstract

Introduction: Whether a specific new antidiabetic drug class reduces cardiovascular events better is uncertain because of few direct comparative trials. We therefore compared new antidiabetic drug classes with respect to cardiovascular outcomes by using network meta-analysis. Methods: Cardiovascular outcome trials or renal outcome trials evaluating cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose co-transporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes were searched up to 30 July 2019. Network meta-analysis was performed using R statistics. Results: Fifteen trials were finally included. Compared to placebo, GLP-1 RAs and SGLT-2 inhibitors significantly reduced major adverse cardiovascular events (odds ratio [OR]=0.88, 95% confidence interval [CI]=0.83-0.93 and OR=0.88, 95% CI=0.82-0.94), cardiovascular mortality (OR=0.89, 95% CI=0.80-0.99 and OR=0.82, 95% CI=0.73-0.92), all-cause mortality (OR=0.90, 95% CI=0.83-0.96 and OR=0.84, 95% CI=0.77-0.92), and renal composite outcome (OR=0.81, 95% CI=0.75-0.88 and OR=0.59, 95% CI=0.52-0.67), respectively. Furthermore, both of the two drug classes reduced major adverse cardiovascular events (OR=0.88, 95% CI=0.80-0.96 and OR=0.88, 95% CI=0.79-0.97), all-cause mortality (OR=0.88, 95% CI=0.79-0.99 and OR=0.83, 95% CI=0.73-0.94), and renal composite outcome (OR=0.78, 95% CI=0.66-0.92 and OR=0.57, 95% CI=0.47-0.68) more than DPP-4 inhibitors. Only SGLT-2 inhibitors reduced hospitalised heart failure when compared with GLP-1 RAs (OR=0.73, 95% CI=0.63-0.85), DPP-4 inhibitors (OR=0.64, 95% CI=0.55-0.75), and placebo (OR=0.68, 95% CI=0.61-0.77). Conclusion: Both GLP-1 RAs and SGLT-2 inhibitors show favourable cardiovascular efficacy and safety profiles while DPP-4 inhibitors do not. Sodium-glucose co-transporter inhibitors reduce cardiovascular events, hospitalised heart failure, renal events, and deaths the most, so they are the preferred treatment for most patients with type 2 diabetes while GLP-1 RAs can be considered thereafter as an add-on therapy.