Objective: To review the literature and describe the pharmacologic, pharmacokinetic, and pharmacodynamic properties; clinical safety; and efficacy of dapagliflozin, a new drug currently under review by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes.
Data sources: A MEDLINE (1995-November 2011) and ClinicalTrials.gov search was conducted using the terms dapagliflozin, sodium-glucose cotransporter 2 inhibitor, and SGLT2 inhibitor. Reference citations from publications identified were also reviewed.
Study selection and data extraction: All English-language studies, including abstracts, evaluating dapagliflozin use in humans were included in this review.
Data synthesis: Dapagliflozin is the first-in-class oral sodium-glucose cotransporter 2 (SGLT2) inhibitor that represents a new potential therapeutic option for the treatment of type 2 diabetes mellitus. Its mechanism of action is insulin- and insulin-sensitivity independent. Preliminary data suggest that dapagliflozin decreases hemoglobin A(1c), fasting plasma glucose, and postprandial plasma glucose, while also promoting weight loss. In Phase 1, 2, and 3 clinical trials, dapagliflozin has exhibited a safety and tolerability profile similar to that of placebo.
Conclusions: Dapagliflozin is a novel oral antihyperglycemic agent that has demonstrated promise as monotherapy and as synergistic combination therapy with currently available agents in Phase 3 clinical trials. On January 19, 2012, the FDA issued a complete response letter to AstraZeneca and Bristol-Myers Squibb regarding the new drug application for dapagliflozin. The FDA is requesting additional clinical data-from ongoing studies and potentially new clinical trials-to better describe the risk-benefit profile of the drug. Both manufacturers remain committed to the development of dapagliflozin, and there are currently 8 Phase 3 trials ongoing. Dapagliflozin has the potential to be the next new oral agent in the diabetes drug armamentarium.