Thiazolidinediones in type 2 diabetes--have they lived up to expectations?

The thiazolidinediones have been in clinical use for the management of type 2 diabetes for the past five years. These agents reduce insulin resistance by acting as ligands that regulate gene expression related to the proliferation and differentiation of adipose tissue. Overall, data from several clinical studies suggest that their hypoglycaemic efficacy is slightly less than sulphonylureas and metformin but greater than acarbose and the glinides. In the short term, treatment with thiazolidinediones is associated with weight gain, expansion of plasma volume, fluid retention, peripheral oedema, an increased risk of congestive heart failure when combined with insulin, and an idiosyncratic hepatotoxic reaction to troglitazone. The long term consequences of these effects are not known. Contrary to expectations, despite being insulin sensitisers these agents do not favourably influence the other components of the metabolic syndrome that are believed to be aggravated by insulin resistance. Dyslipidaemia and elevated blood pressure, which are major risk factors of cardiovascular disease in type 2 diabetes, are not favourably improved with thiazolidinedione treatment. Unlike the sulphonylureas and metformin, which have been shown in recent long term randomised studies to reduce cardiovascular risk substantially, there is no data on the long term cardiovascular safety of the thiazolidinediones. At present, in the absence of long term data, the thiazolidinediones in clinical use are moderately effective hypoglycaemic drugs with no particular advantage over existing treatments in type 2 diabetes.