[Thiazolidinediones: clinical data and perspectives]

Abstract

This brief review realizes a synthesis of the main clinical studies of the three thiazolidinediones (TZDs) which have been launched elsewhere, troglitazone, rosiglitazone and pioglitazone. At optimal dose, the three molecules have a similar effect, although slightly weaker for the first, on the fasting plasma glucose and HbA1c levels. They exhibit identical activity, or even higher for troglitazone, in combination with sulfonylureas, metformine and insulin. On the contrary, the three TZDs seem to differentiate according to their effects on lipid metabolism. While rosiglitazone only moderately and inconstantly reduces plasma triglycerides, troglitazone and pioglitazone decreases them by 15 to 25%. LDL-cholesterol levels are almost unaffected by pioglitazone while they increase by 6 to 8% with troglitazone and by more than 10% with rosiglitazone. On the other hand, HDL-cholesterol strongly increases with rosiglitazone and pioglitazone and only slightly on troglitazone. Besides these metabolic effects, TZDs have several properties which could be of therapeutical interest, particularly a possible beta cell protective effect. Except for the severe problems of hepatotoxicity which appear specific to troglitazone and have led to its withdrawal, TZDs are well tolerated. They share as major undesirable effects a risk of peripheral oedema, of anemia due to plasma volume expansion and of weight gain due to the development of subcutaneous adipose tissue. Until now, the European Product licence of rosiglitazone and pioglitazone is limited to the combination with metformin in case of failure of a monotherapy with metformin in obese type 2 diabetic patients and to the combination with a sulphonylurea only in case of intolerance or contra-indication to metformin in type 2 diabetics insufficiently controlled by sulphonylurea therapy at maximal tolerated dose. These indications will probably be enlarged to earlier treatments when long term study results will be available.