Cardiovascular safety of a novel antihyperglycemic drug as compared to placebo is one of the key criteria required for its approval. Empagliflozin, an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), is the first but not the only antihyperglycemic drug that was superior to placebo in terms of cardiovascular safety (EMPA-REG OUTCOME trial). To date, cardioprotective effect of empagliflozin is supposed to be due both to its diuretic and antihypertensive action and beneficial impact on left ventricular function and myocardial energy metabolism. Liraglutide (LEADER trial) and semaglutide (SUSTAIN-6 trial), glucagon-like peptide-1 (GLP-1) receptor agonists, have also shown superiority to placebo in terms of cardiovascular safety. Their cardioprotective effect is supposed to be specific to all GLP-1 agonists and is explained mostly by weight loss, a reduction of reperfusion injury in acute coronary syndrome, a slight decrease of blood pressure and increase of natriuresis, and endothelial function improvement. Overall, the probable mechanisms of cardiovascular risk reduction by SGLT-2 inhibitors and GLP-1 agonists are similar, despite the difference in pharmacodynamics.
Empagliflozin, liraglutide, semglutide, cardiovascular risk.