The pleiotropic cardiovascular effects of sodium-glucose cotransporter-2 inhibitors

Throughout the history of medicine, scientists and clinicians have observed unanticipated drug effects leading at times to an entirely new use for a drug class, and other times eliminating them from practice. The sodium-glucose cotransporter-2 (SGLT2) inhibitors are one such class of drugs. These agents were initially studied as diabetic agents and their unanticipated and significant cardiovascular benefit has now created a new class of drugs for an entirely new population. Here we review the pleiotropic cardiovascular effects of SGLT2 inhibitors, the potential mechanisms of action, side effect profile and future directions.

Large clinical trials have evaluated the cardiovascular outcomes of SGLT2 inhibitors including myocardial infarction and strokes as well as new onset and worsening systolic heart failure.

SGLT2 inhibitors are being incorporated into the guidelines for the treatment of heart failure with the goal of preventing heart failure hospitalizations and promoting positive ventricular remodeling in patients with or without diabetes. The reduction in cardiovascular events including cardiovascular death, myocardial infarction, and other atherosclerotic effects appears to be driven by baseline risk with those who have known atherosclerosis seeing a reduction in events but those without disease seeing less benefit.