Sodium glucose co-transporter 2 (SGLT2) inhibitors as potential antidiabetic agents

Sodium glucose co-transporter 2 (SGLT2) plays a key role in maintaining glucose equilibrium in the human body. SGLT2 is a kidney transporter that reabsorbs glucose from the renal filtrate and prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 cause the renal excretion of glucose. This observation has led to the hypothesis that SGLT2 inhibitors could be effective agents in the normalisation of high blood glucose levels that are associated with diseases such as Type 1 and Type 2 diabetes. With this goal in mind, a number of pharmaceutical companies have launched medicinal chemistry programmes directed towards the discovery of novel SGLT2 inhibitors. Several organisations have described potent and selective SGLT2 inhibitors that belong to a class of structurally-related aromatic C-, N- and O-beta-D-glucopyranoside analogues of the natural product phlorizin. This review will highlight some of the advances that have been made in the discovery of SGLT2 inhibitors and discuss their potential as effective treatments for Type 2 diabetes and other diseases.