Dapagliflozin. SGLT2 inhibitor, Antidiabetic agent

Diabetes is a growing epidemic for which new treatments are needed as it is often not controlled with current therapies. One potential means of treating diabetes is via modulation of glucose uptake. A novel strategy for achieving this is through inhibition of sodium-dependent glucose transporters (SGLTs), which mediate the process by which plasma glucose filtered in the kidney glomerulus is reabsorbed. The great majority of this process of reabsorption is mediated by Si and SGLT2 inhibitors have therefore been sought and identified in order to prevent renal glucose reabsorption and increase glucose excretion in urine. The compound that has advanced the furthest is dapagliflozin, which demonstrated superior metabolic stability compared to early agents. Dapagliflozin also exhibited potent inhibition of SGLT2 and selectivity over SGLT1 in vitro, and was associated with reduced plasma glucose levels in animal models of diabetes after acute and chronic dosing. Dapagliflozin has proven safe and well tolerated in humans, with pharmacokinetic and pharmacodynamic variables indicating that daily dosing is appropriate. Double-blind trials in patients with type 2 diabetes revealed reductions in fasting and postprandial glucose, as well as significant reductions in HbA1c. Dapagliflozin has entered phase III evaluation.