The potential role of sodium glucose co‐transporter 2 inhibitors in the early treatment of type 2 diabetes mellitus

BACKGROUND Sodium glucose co-transporter 2 (SGLT2) inhibitors are a new class of pharmacologic agents developed for the treatment of type 2 diabetes mellitus (T2DM). Their unique mechanism of action is independent of pancreatic beta-cell function or the degree of insulin resistance, giving these agents the potential for use in combination with any of the existing classes of glucose-lowering agents, including insulin. This makes SGLT2 inhibitors an option for patients with long-standing T2DM, but they also have a promising role for early intervention in T2DM, and that role is explored in this review. METHODS A literature search was performed to identify relevant English language articles relating to SGLT2 inhibitors, particularly dapagliflozin, canagliflozin and empagliflozin. RESULTS Clinical trials of dapagliflozin, canagliflozin and empagliflozin, given as monotherapy or in combination with other glucose-lowering agents, reported clinically significant improvements in glycaemic control, body weight and systolic blood pressure. SGLT2 inhibitors were well tolerated and had a generally favourable safety profile. Few serious adverse events have been reported to date. The frequency of hypoglycaemic events was low, similar to that of placebo, and the choice of co-administered glucose-lowering agent was the major determinant of hypoglycaemic risk. Increased genital and urinary tract infections were consistently reported with SGLT2 inhibitors. CONCLUSIONS SGLT2 inhibitors, with their unique insulin-independent mode of action, could have a significant impact on the early management of T2DM, by addressing some of the specific risk factors associated with this disease. SGLT2 inhibitors induce beneficial changes in a number of cardiovascular risk factors, such as lowering blood pressure and body weight, in addition to improved glycaemic control, although information on clinical cardiovascular outcomes is currently limited.