Author(s): DeFronzo RA, AbdulGhani MA
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Abstract CONTEXT: The Centers for Disease Control and Prevention estimates that there are approximately 79,000,000 individuals in the United States with prediabetes [impaired glucose tolerance (IGT) and/or impaired fasting glucose] and that approximately 40-50\% will progress to type 2 diabetes mellitus (T2DM) during their lifetime. Therefore, treatment of high-risk IGT individuals to prevent T2DM has important medical, economic, social, and human implications. Individuals in the upper tertile of IGT are maximally/near-maximally insulin resistant, have lost 70-80\% of their β-cell function, and have approximately a 10\% incidence of diabetic retinopathy. Therefore, preservation of the remaining 20-30\% of β-cell function is critical to prevent future development of T2DM. EVIDENCE ACQUISITION: We searched MEDLINE from 2000 to the present to identify placebo-controlled trials in which individuals with IGT received pharmacological therapy to prevent progression to diabetes. EVIDENCE SYNTHESIS: Lifestyle modification reduces IGT conversion to T2DM, but it is difficult to implement and maintain. Moreover, 40-50\% of IGT subjects progress to T2DM despite weight loss. In contrast, pharmacological intervention with medications that reverse known pathophysiological abnormalities (β-cell dysfunction and insulin resistance) uniformly prevents IGT progression to T2DM. Thiazolidinediones reduce IGT conversion to diabetes by approximately 50-70\%. Metformin in the U.S. Diabetes Prevention Program reduced the development of T2DM by 31\% and has been recommended by the American Diabetes Association. Because glucagon-like peptide-1 analogs augment insulin secretion, preserve β-cell function, and promote weight loss, they may be efficacious in preventing IGT progression to T2DM. CONCLUSION: Pharmacological intervention with a variety of agents (thiazolidinediones, metformin, acarbose, glucagon-like peptide-1 analogs) consistently reduces the rate of conversion of IGT to T2DM.
This article was published in J Clin Endocrinol Metab
and referenced in Journal of Molecular and Genetic Medicine