Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance

作者：Ralph A. DeFronzo, Devjit Tripathy, Dawn C. Schwenke, MaryAnn Banerji, George A. Bray, Thomas A. Buchanan, Stephen Clement, Robert R. Henry, Howard N. Hodis, Abbas E. Kitabchi, Wendy J. Mack, Sunder Mudaliar, Robert E. Ratner, Ken Williams, Frankie B. Stentz, Nicolas Musi, Peter D. Reaven · 发表于：New England Journal of Medicine · 年份：2011 · DOI：10.1056/nejmoa1010949 · 被引用次数：752 · 研究领域：Diabetes, Cardiovascular Risks, and Lipoproteins、Diabetes Treatment and Management、Peroxisome Proliferator-Activated Receptors

BACKGROUND: Impaired glucose tolerance is associated with increased rates of cardiovascular disease and conversion to type 2 diabetes mellitus. Interventions that may prevent or delay such occurrences are of great clinical importance. METHODS: We conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing. RESULTS: Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16 to 0.49; P<0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (P<0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg per deciliter vs. 8.1 mg per deciliter [0.7 mmol per liter vs. 0.5 mmol per liter], P<0.001), 2-hour glucose (a decrease of 30.5 mg per deciliter vs. 15.6 mg per deciliter [1.6 mmol per liter vs. 0.9 mmol per...