Sodium–glucose Cotransporter 2 Inhibitors’ Rise to the Backbone of Heart Failure Management: A Clinical Review

Sodium–glucose cotransporter (SGLT) 2 inhibitors, or gliflozins, have quickly risen to prominence within the cardiovascular field due to their substantial benefit in the management of heart failure with reduced ejection fraction (HFrEF). SGLT channels are present throughout the body in various isoforms, but SGLT1 and SGLT2 have been the centre of medical investigation due to known genetic mutations. SGLT2 plays a major role in renal re-absorption of glucose, prompting the development of SGLT2 inhibitors to promote glycosuria and aid in diabetes management. The United States Food and Drug Administration requires evaluation of new antidiabetic medications for cardiovascular safety, prompting several randomized controlled trials of SGLT2 inhibitors over the past 5 years. These initial trials demonstrated superiority in cardiovascular outcomes with SGLT2 inhibitor use and suggested particular benefit in heart failure (HF) outcomes, prompting further study of their mechanisms. Subsequent SGLT2 inhibitor studies have demonstrated reductions in HF hospitalizations and cardiovascular mortality in patients with HFrEF, regardless of the presence of diabetes mellitus. In this review, we discuss the mechanism of action and major clinical trial results that have propelled SGLT2 inhibitors into a key role for patients with HFrEF.