SGLT2 inhibitors in heart failure with reduced ejection fraction

Sodium – glucose co-transporter 2 (SGLT2) inhibitors reduce blood glucose by inhibiting reabsorption of glucose from the proximal renal tubules. Initial studies showed that apart from reducing blood glucose they also reduce the combined endpoint of myocardial infarction, stroke, and cardiovascular death, hospitalization from heart failure, and occurrence of renal failure in patients with known cardiovascular disease or at high risk of developing cardiovascular disease. Recent studies have shown that these drugs also could be used in patients to treat heart failure or to slow the progression of renal failure, irrespective of whether the patients have diabetes or not. In this review, we discuss the clinical trial evidence for the use of SGLT2 inhibitors for the treatment of patients with heart failure with reduced ejection fraction and for the prevention of heart failure in patients with diabetes who are at high risk of cardiovascular events. We also discuss the plausible mechanisms of action for the cardiovascular beneficial effects of SGLT2 inhibitors. EMPA-REG OUTCOME TRIAL, DECLARE-TIMI 58, CANVAS, VERTIS-CV studies have shown that SGLT2 inhibitors namely empagliflozin, dapagliflozin, canagliflozin and ertugliflozin reduce the chances of hospitalisation in patients who have cardiovascular disease or at high risk of cardiovascular disease. The DAPA-HF study and the EMPEROR-REDUCED TRIAL have further shown that Dapagliflozin and Empagliflozin could be used to treat patients with heart failure, with or without diabetes. SGLT2 inhibitors provide us with a new armamentarium for treatment of patients with a triad of diabetes, heart or renal disease. Their mechanism of action in prevention or treatment of patients with heart failure however still remains speculative.