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.