Dapagliflozin for the Treatment of Type 2 Diabetes

被引:29
作者
Anderson, Sarah L. [1 ]
Marrs, Joel C. [1 ]
机构
[1] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA
关键词
dapagliflozin; SGLT2; inhibitor; sodium-glucose cotransporter 2 inhibitor; type 2 diabetes mellitus; INADEQUATE GLYCEMIC CONTROL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; HEALTHY-SUBJECTS; SGLT2; INHIBITOR; PHARMACOKINETICS; GLIMEPIRIDE; GLUCOSURIA; METFORMIN; MELLITUS;
D O I
10.1345/aph.1Q538
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:590 / 598
页数:9
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