Sodium glucose cotransporter (SGLT)-2 inhibitors: Do we need them for glucose-lowering, for cardiorenal protection or both?

Sodium glucose cotransporter (SGLT)-2 inhibitors are the newest addition to our treatment armamentarium for the management of hyperglycemia in type 2 diabetes. Glucose-lowering per se reduces the risk of microvascular complications, but not the risk of cardiovascular disease, including heart failure and cardiovascular mortality. Also, even when embedded in optimal cardiovascular prevention, a large residual risk remains with respect to progression of diabetic kidney disease. SGLT-2 inhibitors lower blood glucose levels by inducing glucosuria. Through various proposed mechanisms, among which diuretic and natriuretic effects, SGLT-2 inhibitors decrease heart failure hospitalization, reduce cardiovascular mortality, and mitigate progression of diabetic kidney disease. In this perspective, we will discuss the glucose-lowering and other protective effects of SGLT-2 inhibitors on the cardiorenal axis, both in primary and secondary prevention. By comparing the glycemic and pleiotropic effects of these agents to other glucose-lowering drugs, we will address questions around whether SGLT-2 inhibitors should be considered primarily as glucose-lowering agents, cardiorenal drugs or both.