Dapagliflozin for the treatment of type 2 diabetes.

OBJECTIVE: To review the literature and describe the pharmacology, pharmacokinetics, clinical safety, and efficacy of dapagliflozin, a compound currently in Phase 3 clinical trials.

DATA SOURCES: A search of the literature was conducted via MEDLINE (1995-March 2009) and ClinicalTrials.gov using the search terms dapagliflozin, SGLT2 inhibitor, sodium-glucose co-transport inhibition, and renal glucose reabsorption inhibition. Bibliographies of identified articles were also used to identify useful references.

STUDY SELECTION AND DATA EXTRACTION: All English-language reports evaluating dapagliflozin were included in this review, including abstracts and scientific presentations.

DATA SYNTHESIS: Due to the increasing prevalence of type 2 diabetes, suboptimal management of the associated hyperglycemia, morbidity and mortality associated with the disease, and the limitations of currently available therapies, novel therapeutic strategies are needed for its treatment. Dapagliflozin represents the first selective, sodium-glucose cotransporter 2 inhibitor that functions by regulating renal glucose reabsorption. Clinical trial data are limited, but available evidence supports clinically significant reductions in fasting plasma glucose, postprandial plasma glucose, hemoglobin A(1c), and body weight with this agent. In addition, dapagliflozin has demonstrated excellent tolerability with safety data demonstrated in both Phase 1 and Phase 2 studies.

CONCLUSIONS: Dapagliflozin represents the first in a new class of drugs that may represent a promising new option in the treatment of type 2 diabetes. Results of ongoing Phase 3 clinical trials are necessary to demonstrate efficacy and safety of this agent across various patient populations and clinical scenarios.