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

Type II diabetes is a polygenic disorder, characterized in most cases by ea rly onset of resistance to the action of insulin. Insulin sensitizers belon ging to the thiazolidinedione class offer the first therapeutic option spec ifically targeting the underlying insulin resistance. Troglitazone is the p rototype drug of this class and has been approved for marketing in several countries. Troglitazone offers several benefits over traditional oral hypog lycemic agents such as sulfonylureas and the biguanide metformin. Most of t hese advantages are related to better control of glycemic parameters with t roglitazone alone or when added to existing treatment. In addition, it has interesting lipid lowering activity that may be of potential benefit in red ucing morbidity from cardiovascular disease among diabetics. However, trogl itazone may not be the ideal insulin sensitizer since 20-30% of diabetics d o not respond to it. Also, it produces liver toxicity in 2% of patients, ne cessitating withdrawal of the drug. A number of second generation insulin s ensitizers, belonging to the same chemical class as troglitazone, are in cl inical development. The role of insulin sensitizers in the management of di abetes and other diseases in which insulin resistance is an underlying feat ure, is likely to undergo evolution as more information is obtained from cl inical studies.