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A paradigm shift in diabetes therapy--dapagliflozin and other SGLT2 inhibitors.

Blocking sodium-glucose cotransporters (SGLTs) to decrease the reabsorption of glucose--and thus increase renal glucose excretion--represents a novel therapeutic approach to diabetes that is independent of insulin secretion or action. Preclinical and clinical studies of SGLT2 inhibitors in subjects with type 2 diabetes (T2DM), as well as genetic mutations in kidney-specific SGLT2 that result in no adverse sequelae, appear to support this strategy. These investigations reveal that increasing renal glucose excretion by inhibiting SGLT2 can lower plasma glucose levels, as well as reduce body weight. Further data from larger trials are forthcoming regarding efficacy and safety, but the results reported thus far suggest that the positive impact of SGLT2 inhibitors may be attained without producing significant adverse effects. This class of agents, including dapagliflozin, may thus hold an advantage over many currently used medications for diabetes. This review outlines the role of SGLT2 in glucose homeostasis and the evidence currently available on the potential for clinical application of these agents in diabetes.