Effects of thiazolidinediones for early treatment of type 2 diabetes mellitus.

The thiazolidinediones (TZDs) are a new class of oral antidiabetic agents used in the treatment of type 2 diabetes mellitus. TZDs are selective and potent agonists of peroxisome proliferator-activated receptor-gamma, which is expressed in target tissues for insulin action and in a variety of cells that play an important role in atherosclerosis. TZDs primarily improve glycemic control by reducing insulin resistance in target tissues. Evidence also suggests that the TZDs may have a direct, beneficial effect on beta-cell function. In patients with impaired glucose tolerance (prediabetics), treatment with a TZD improves insulin secretory responses and proinsulin concentrations. These beta-cell-specific effects may result in prolongation of beta-cell function and the enduring glycemic control necessary to prevent microvascular complications. Durable glycemic control has not been clearly demonstrated with other antihyperglycemic agents. The TZDs may prevent or delay the macrovascular complications associated with type 2 diabetes. TZDs improve the characteristic dyslipidemia of type 2 diabetes, promote decreases in blood pressure, and enhance fibrinolysis. In addition, they exert direct effects on the vasculature, including the ability to decrease the intimal medial thickness and inhibit transendothelial migration of monocytes. These demonstrated antiatherogenic effects may reduce the cardiovascular complications commonly associated with type 2 diabetes. TZDs also reduce microalbuminuria to a greater extent than other agents. Use of a TZD early in the course of therapy may reduce the risk of development of many of the long-term microvascular and macrovascular complications associated with type 2 diabetes.