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.