SGLT2 inhibitors: hypotheses on the mechanism of cardiovascular protection

Diabetes is an important cardiovascular risk factor, but until recently a disconnect has existed between management of type 2 diabetes and reduction of cardiovascular mortality and morbidity. Such was the mixed impact of previous generations of antihyperglycaemic drugs that the US and European drug regulators mandated cardiovascular outcome studies to assess the safety of all future therapeutic interventions. Somewhat ironically, this move unveiled an unexpected but welcome cardiovascular benefit with some newer generation drugs, including the sodium-glucose co-transporter-2 (SGLT2) inhibitors. Much has already been written regarding the reduction of cardiovascular death in patients with, or at high risk of developing, coronary artery disease, and there has been much speculation regarding the mechanism of cardioprotection with respect to blood pressure reduction, diuresis, and weight loss. 1 Heerspink HJ Perkins BA Fitchett DH Husain M Cherney DZ Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016; 134: 752-772 Crossref PubMed Scopus (742) Google Scholar However, these drugs might also have additional, potentially pleiotropic effects that underlie their cardioprotective outcomes.