The role of sodium-glucose co-transporter (SGLT)-2 inhibitors in heart failure management and implications for the kidneys.

Sodium-glucose co-transporter (SGLT)-2 inhibitors were initially developed for management of type 2 diabetes but have been shown to offer improved outcomes in heart failure, a condition in which concomitant chronic kidney disease (CKD) is common. Randomised controlled trials initially demonstrated prognostic cardiovascular and renal benefits of SGLT2 inhibitors in high cardiovascular risk individuals with type 2 diabetes particularly in relation to heart failure. Improved outcomes have been replicated in cohorts with established heart failure and/or CKD and appear to extend in those without diabetes. Several specific agents have been considered, with evidence of a class effect, and dapagliflozin and empagliflozin are now incorporated into major international cardiovascular guidelines for management of heart failure with reduced ejection fraction. Beyond glucose lowering effects the mechanisms mediating SGLT2 inhibitors favourable actions are not fully elucidated. Haemodynamic alterations, natriuresis, osmotic diuresis, and weight loss likely contribute to improved outcomes, along with an enhanced cardiometabolic profile. The functional drop in estimated glomerular filtration rate (eGFR) which accompanies SGLT2 inhibitor initiation, before eGFR stabilisation, is likely central in the observed renal benefits. In this review we discuss in detail the evidence for SGLT2 inhibitors in heart failure, particularly with regard to kidney health.