New antihyperglycaemic agents and cardiovascular disease: let's be optimistic.

Abstract

Cardiovascular disease (CVD) substantially increases mortality in diabetes mellitus. This narrative review highlights recent research on the putative associations between dipeptyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose co-transporter 2 inhibitors (SGLT-2is) and several cardiovascular risk factors. New antihyperglycaemic agents favourably modulate several CVD risk factors, including fasting and postprandial plasma glucose levels, body weight, blood pressure, lipids, microalbuminuria, nonalcoholic fatty liver disease, serum uric acid, and arterial stiffness. Liraglutide (in LEADER), semaglutide (in SUSTAIN-6), empagliflozin (in EMPA-REG OUTCOME), and canagliflozin (in CANVAS) were all associated with reduction of the primary composite outcome (i.e. cardiovascular death, nonfatal myocardial infarction or stroke). Of note, patients at higher CVD risk, with optimally controlled CVD risk factors seem to benefit more. Recent trials with SGLT-2is and GLP-1RAs show superiority in CVD event reduction as opposed to only noninferiority. It is still unclear if the results can be generalised to the lower risk population with diabetes but without CVD. Head-to-head comparison and CVD outcome trials involving combination of these two drug classes are also expected to facilitate decision making in clinical practice.