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There are now a variety of oral agents available to treat type 2 diabetes. As shown on the slide, these agents have various therapeutic targets. Newer agents, such as the thiazolidinediones, address insulin resistance at the skeletal muscle. Metformin inhibits gluconeogenesis in the liver and reduces hepatic glucose production. Acarbose and miglitol decrease glucose absorption from the gut.

However, the preceding studies (id, UKPDS 16 and Weyer C, et al, 1999) highlight the importance of beta-cell dysfunction in type 2 diabetes. Beta-cell dysfunction needs to be addressed with insulin secretagogues or insulin.

This is one reason why sulfonylureas have long been a mainstay of antidiabetes therapy, since these agents enhance insulin secretion.

UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16. Overview of 6 years’ therapy of type II diabetes: a prospective disease. Diabetes. 1995;44:1249-1258.

Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104:787-794.

DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131:281-303.