From history to reality: sodium glucose co‐transporter 2 inhibitors – a novel therapy for type 2 diabetes mellitus

Abstract

The human kidney has a key role in the regulation of blood glucose predominantly by reabsorption of glucose from the glomerular filtrate via sodium glucose co‐transporter 2 (SGLT‐2) channels. These are expressed in the proximal renal tubules and are blocked by SGLT‐2 inhibitors, which are novel pharmacological agents currently in development. Specific SGLT‐2 inhibition results in significant increases in renal glucose excretion causing a net calorie loss and consequent weight loss, coupled with a lowering of blood glucose due to removal of glucose from the circulation. The main side effect of SGLT‐2 inhibitors appears to be an increase in genital infections, although concerns remain about the potential adverse effects of dehydration and electrolyte imbalance. Dapagliflozin is the SGLT‐2 inhibitor that is the furthest along in development, and is currently in phase III clinical trials.In this review article we consider the role of the kidney in glucose homeostasis in normal and diabetic subjects. We also review the history and concept of SGLT‐2 inhibition, and discuss the future potential clinical utility of this promising new class of drugs. Copyright © 2010 John Wiley & Sons.