Thiazolidinediones: clinical data and perspectives

This brief review realizes a synthesis of the main clinical studies of the three thiazolidinediones (TZDs) which have been launched elsewhere, troglit azone, rosiglitazone and pioglitazone. At optimal dose, the three molecules have a similar effect, although slightly weaker for the first, on the fast ing plasma glucose and HbA1c levels. They exhibit identical activity, or ev en higher for troglitazone, in combination with sulfonylureas, metformine a nd insulin. On the contrary, the three TZDs seem to differentiate according to their effects an lipid metabolism. While rosiglitazone only moderately and inconstantly reduces plasma triglycerides, troglitazone and pioglitazon e decreases them by 15 to 25 %. LDL-cholesterol levels are almost unaffecte d by pioglitazone while they increase by 6 to 8 % with troglitazone and by more than 10 % with rosiglitazone. On the other hand, HDL-cholesterol stron gly increases with rosiglitazone and pioglitazone and only slightly on trog litazone. Besides these metabolic effects, TZDs have several properties which could b e of therapeutical interest, particularly a possible beta cell protective e ffect. Except for the severe problems of hepatotoxicity which appear specific to t roglitazone and have led to its withdrawal, TZDs are well tolerated. They s hare as major undesirable effects a risk of peripheral oedema, of anemia du e to plasma volume expansion and of weight gain due to the development of s ubcutaneous adipose tissue. Until now, the European Product licence of rosiglitazone and pioglitazone i s limited to the combination with metformin in case of failure of a monothe rapy with metformin in obese type 2 diabetic patients and to the combinatio n with a sulphonylurea only in case of intolerance or contraindication to m etformin in type 2 diabetics insufficiently controlled by sulphonylurea the rapy at maximal tolerated dose. These indications will probably be enlarged to earlier treatments when long term study results will be available.