The Sweet Spot: Heart Failure Prevention with SGLT2 Inhibitors

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of medications that reduce plasma glucose concentrations through an insulin-independent mechanism of increased urinary glucose excretion, with concomitant natriuresis and diuresis. Clinical outcomes trials with SGLT2 inhibitors revealed a cardioprotective benefit among patients with diabetes mellitus, with a consistent reduction in hospitalization for heart failure. As such, the 2018 updated US and European treatment guidelines for diabetes mellitus incorporated SGLT2 inhibitors as second-line glucose-lowering agents after metformin. Although well tolerated, there are known adverse effects with SGLT2 inhibitors that require clinical monitoring, such as genital mycotic infections, diabetic ketoacidosis, volume depletion particularly in the setting of concomitant diuretic use, and lower limb amputations with canagliflozin. Ongoing clinical trials will uncover the potential benefit of SGLT2 inhibitors in patients with prevalent heart failure with or without diabetes mellitus.