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Korean Diabetes J. 2010 Dec;34(6):331-337. English. Review.
Kim SW .
Diabetes Center, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Although there is no HbA1c threshold for cardiovascular risk, the American Diabetic Association-recommended goal of HbA1c < 7.0% appears to be unacceptably high. To achieve an optimal HbA1c level goal of 6.0% or less, a high dosage of sulfonylureas and insulin would be required; the trade-off would be the common adverse effects of hypoglycemia and weight gain. In contrast, hypoglycemia is uncommon with insulin sensitizers and GLP-1 analogs, allowing the physician to titrate these drugs to maximum dosage to reduce HbA1c levels below 6.0% and they have been shown to preserve beta-cell function. Lastly, weight gain is common with sulfonylurea and insulin therapy, whereas GLP-1 analogs induce weight loss and offset the weight gain associated with TZDs. A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which has antiatherogenic effects and improves hepatic insulin sensitivity), a TZD (which improves insulin sensitivity and preserves beta-cell function with proven durability), and a GLP-1 analog (which improves beta, alpha-cell function and promotes weight loss) or a dipeptidyl peptidase IV inhibitor in patients with type 2 diabetes mellitus.

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