PMID: 19943222Nov 28, 2009Paper

Dapagliflozin, an oral sodium glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.

IDrugs : the Investigational Drugs Journal
Joaquim Calado

Abstract

Dapagliflozin (BMS-512148), a specific inhibitor of the sodium-glucose cotransporter SGLT2, is under development by AstraZeneca plc and Bristol-Myers Squibb Co for the potential oral treatment of type 2 diabetes mellitus (T2DM); a fixed-dose combination of dapagliflozin and metformin is also being developed by the companies for the potential treatment of diabetes mellitus. Phlorizin, a naturally occurring O-glucoside, inhibits renal glucose transport and induces glucosuria in rodent models of diabetes; however, phlorizin inhibits other glucose transporters in addition to SGLT2 and thus is not suitable for oral administration. The chemical synthesis of more specific SGLT2 inhibitors led to the identification of dapagliflozin, a C-aryl glucoside that was highly selective for SGLT2 compared with SGLT1. In phase II clinical trials in patients with T2DM, once-daily dapagliflozin induced dose-dependent increases in glucosuria and efficiently reduced HbA1c, fasting and postprandial glucose levels. Dapagliflozin was not associated with significant hypoglycemic episodes or weight gain; rather, the caloric losses related to renal glucose wasting induced a net weight loss. In addition, the diuretic effect observed with dapagliflozin may h...Continue Reading

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