The emerging role of thiazolidinediones in the treatment of diabetes-mellitus and related disorders.

Abstract

Type II diabetes is a polygenic disorder, characterized in most cases by early onset of resistance to the action of insulin. Insulin sensitizers belonging to the thiazolidinedione class offer the first therapeutic option specifically targeting the underlying insulin resistance. Troglitazone is the prototype drug of this class and has been approved for marketing in several countries. Troglitazone offers several benefits over traditional oral hypoglycemic agents such as sulfonylureas and the biguanide metformin. Most of these advantages are related to better control of glycemic parameters with troglitazone alone or when added to existing treatment. In addition, it has interesting lipid lowering activity that may be of potential benefit in reducing morbidity from cardiovascular disease among diabetics. However, troglitazone may not be the ideal insulin sensitizer since 20-30% of diabetics do not respond to it. Also, it produces liver toxicity in 2% of patients, necessitating withdrawal of the drug. A number of second generation insulin sensitizers, belonging to the same chemical class as troglitazone, are in clinical development. The role of insulin sensitizers in the management of diabetes and other diseases in which insulin resistance is an underlying feature, is likely to undergo evolution as more information is obtained from clinical studies.