The role of thiazolidinediones in the treatment of patients with type 2 diabetes mellitus.

Diabetes mellitus is a significant and growing health concern worldwide. Unfortunately, type 2 diabetes mellitus is generally under-managed, and this may explain the increasing prevalence of diabetic complications throughout the world. The introduction of newer classes of antihyperglycemic agents should enhance the ability of clinicians to achieve optimal blood glucose control. One recent addition to the pharmacologic armamentarium is the thiazolidinedione class. The main effect of thiazolidinediones is amelioration of insulin resistance. These agents may also preserve beta-cell function, although evidence in favor of this effect is still inconclusive. The mechanism of action of thiazolidinediones is not completely understood. Similarly, the current state of knowledge cannot explain the differences in the lipid effects of pioglitazone and rosiglitazone. Thiazolidinediones are commonly used as add-on therapy for those requiring large daily doses of insulin therapy, or in addition to sulfonylurea agents and metformin for those reluctant to start insulin therapy. The potential role of thiazolidinediones as first-line therapy is now emerging. It is possible that in certain subgroups, particularly patients with renal failure, elderly individuals or those with corticosteroid-induced diabetes mellitus, the use of thiazolidinediones as a first-line therapy is justifiable. However, the lack of a long-term safety record, and the cost, would limit the widespread acceptance of this class of agents as first-line therapy.