Section Review: Oncologic, Endocrine & Metabolic: Thiazolidinediones

Abstract

To date, the treatment of Non-Insulin Dependent Diabetes Mellitus (NIDDM) has focused primarily on attempts to correct some of the metabolic abnormalities commonly associated with the disease. Insulin and/or insulin secretagogues, such as sulphonylureas, are frequently used to lower blood sugar; however, there is a significant risk of hypoglycaemia. Moreover, the use of insulin or insulin secretagogues in patients who are already hyperinsulinaemic may accelerate some of the cardiovascular complications of NIDDM, and further aggravate insulin resistance. Other therapeutic strategies have focused on aberrations in glucose metabolism or absorption, including biguanides, such as metformin, or glucosidase inhibitors, such as acarbose. While these agents have been efficacious to a degree, they do not have a direct impact on the underlying pathology of insulin resistance. A novel therapeutic strategy involves the use of insulin-sensitising agents, such as the thiazolidinediones. These compounds appear to improve insulin resistance by enhancing insulin action in skeletal muscle, liver and adipose tissue. Recent preclinical studies have revealed key insights into the potential mechanism of action of the thiazolidinediones. Furthermore, the emerging clinical experience with one of these agents, troglitazone, is substantiating the benefits of these agents in insulin-resistant diseases.