Development of sodium-dependent glucose co-transporter 2 inhibitors as potential anti-diabetic therapeutics.

The kidney plays an important role in the regulation of plasma glucose. It is estimated that greater than 99% of the renal glucose filtered by kidney glomerulus is resorbed by sodium-dependent glucose co-transporters (SGLTs), and that SGLT2 located in the proximal renal tubule achieves the most of this assignment. Studies of SGLT2 inhibitors indicate that raising renal glucose excretion by inhibiting SGLT2 helps effectively normalize the plasma glucose levels in individuals with type 2 diabetes mellitus (T2DM). This review discusses the discovery of SGLT2 inhibitors and the related structure-activity relationship (SAR) studies. The clinical trial data of dapagliflozin is also involved.