TROGLITAZONE - REVIEW AND ASSESSMENT OF ITS ROLE IN THE TREATMENT OF PATIENTS WITH IMPAIRED GLUCOSE-TOLERANCE AND DIABETES-MELLITUS

OBJECTIVE: TO introduce troglitazone (CS-045, Rezulin), a new oral ant idiabetic agent and discuss its pharmacology, therapeutics, pharmacoki netics, dosing guidelines, adverse effects, drug interactions, and cli nical efficacy. DATA SOURCES: A MEDLINE database search was completed to identify relevant articles including reviews, recent studies and ab stracts, and data from Parke-Davis. STUDY SELECTION: Due to the small number of published human studies available, some data are derived fro m animal studies and abstracts of human studies. Studies and abstracts chosen summarize the clinical action of troglitazone in healthy volun teers, in subjects with impaired glucose tolerance, and in patients wi th diabetes mellitus. Three of the six published human studies used su bjects in a placebo-controlled, multicenter, randomized environment (t ype 2 diabetic patients or obese subjects with insulin resistance). DA TA EXTRACTION: All clinical trials available, including unpublished re ports, were reviewed. DATA SYNTHESIS: Troglitazone is the first member of a new class of medications, the thiazolidinediones, to be approved for clinical use. Troglitazone increases insulin sensitivity in skele tal muscle and in hepatic and adipose tissue. It has been shown to dec rease hepatic glucose output while having no effect on stimulating ins ulin secretion from the pancreatic beta-cells. Its metabolic effects d ecrease fasting and postprandial hyperglycemia, insulin concentrations , and triglyceride concentrations, while increasing high-density lipop rotein concentrations. There is some evidence, based on short-term tri als, that troglitazone causes only minimal decreases in glycosylated h emoglobin A(1c) (HbA(1c)) concentrations. Data suggest that troglitazo ne decreases impaired glucose tolerance in nondiabetic obese subjects and leads to a reduction in both systolic and diastolic blood pressure in hypertensive type 2 diabetes mellitus patients. Troglitazone has a mild adverse effect profile, with rare instances of abnormal liver fu nction tests. CONCLUSIONS: Troglitazone appears to be a safe, effectiv e, and useful new agent in the treatment of insulin-requiring type 2 d iabetes mellitus patients, although its HbA(1c)-lowering effects have been minimal in short-term trials, and its insulin dosage-reduction ac tivity remains unclear. The Food and Drug Administration has also appr oved its use as monotherapy and in combination with sulfonylureas for patients with type 2 diabetes. It may have use in the treatment of pat ients with impaired glucose tolerance, but more clinical experience is needed before definitive conclusions can be made. The role of troglit azone therapy in diabetes mellitus and impaired glucose intolerance wi ll continue to evolve as the results of studies and our clinical exper ience with this agent become available.