Sodium-glucose co-transporter 2 inhibitors: A new path for heart failure treatment

Results from cardiovascular outcome trials (CVOT) with 5 different sodium-glucose co-transporter 2 inhibitors (SGLT2i; empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, sotagliflozin), initially developed for their glucose-lowering effect by blocking tubular glucose reabsorption in kidney, have been shown to decrease the risk of heart failure hospitalization (HFH) across a range of patients with and without atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Following these CVOT results, SGLT2i (dapagliflozin, empagliflozin, sotagliflozin) also were reported to reduce HFH and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of existence or absence of T2DM. Ongoing studies have been conducted to evaluate the clinical benefit of SGLT2i (empagliflozin, dapagliflozin) in patients with heart failure with preserved ejection fraction (HFpEF). Although SGLT2i brought us to the entrance of a new era for prevention of HF incidence and worsening of HF, the search for pivotal mechanism of SGLT2i to improve our pharmacological armamentarium should continue in order to protect every HF patient from fatal progression of HF disease. In this review, we summarized the updated clinical evidences on SGLT2i (rather than basic and translational evidence) for reduction of HF risk in T2DM patients and favorable clinical outcomes in both HFrEF and HFpEF patients.