Thiazolidinediones for the treatment of type 2 diabetes

Thiazolidinediones (TZD), or glitazones, represent a new generation of antidiabetic drugs that have recently been introduced in Europe. They improve insulin resistance, one of the key anomalies involved in the pathogenesis of type 2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator activated receptor-gamma (PPAR-gamma), leading to crucial metabolic alterations in adipose tissue. Rosightazone and pioglitazone have been shown to be active as monotherapy, in combination therapy with metformin or sulfonylureas, and even in triple therapy. They are generally well tolerated but can induce fluid retention. Cardiac failure is a contraindication for the use of TZDs, as is the concomitant administration of insulin. Aside from their effect on glycemic control, TZDs act on several cardiovascular risk factors and may protect pancreatic beta cells from apoptosis. The cardiovascular protective effect of TZDs has recently been demonstrated with the results of the PROactive study, and long-term preservation of beta-cell function is currently under further investigation. (C) 2006 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.