Ramping Glucosuria for Management of Type 2 Diabetes Mellitus: An Emerging Cynosure

Chronic hyperglycemia is a characteristic feature of type 2 diabetes mellitus (T2DM). The kidney plays a vital role in maintaining blood glucose homeostasis by recovering glucose from glomerular filtrate which is controlled by SGLT2 cotransporters expressed mainly in proximal tubule. In T2DM patients, inhibition of SGLT2 normalizes glycemic levels by preventing glucose from being reabsorbed through SGLT2 and re-entering the circulation. Thus, SGLT2 inhibition seems to be a logical approach and pose a novel insulin-independent mechanism of action for management of T2DM by promoting urinary glucose excretion in the body. Canagliflozin is the first SGLT2 inhibitor approved by US Food and Drug Administration (US FDA) followed by dapagliflozin while empagliflozin is under FDA review. Various other drug candidates in late-stage clinical developments are also expected to hit the global markets in the coming years. In this review, studies on various early-and late-stage SGLT2 inhibitors have been investigated and recent clinical developments summarized. (C) 2014 Wiley Periodicals, Inc.