Troglitazone

Troglitazone has been found effective in improving glycemic control in type 2 diabetics. It appears to enhance peripheral insulin sensitivity in diabetics as well as in obese, nondiabetic individuals. It is thought to possibly improve B-cell function in those with impaired glucose tolerance as well, implying that it may play a role as a primary prevention method of type 2 diabetes.

University of California researchers attempted to further investigate the metabolic effects of troglitazone in type 2 diabetics, as well as obese and lean individuals, in a recent study. They also evaluated the metabolic effects of troglitazone two to three weeks following discontinuation of this medication in diabetic subjects.

Nine type 2 diabetics, nine obese individuals (BMI [is greater than] 26 kg/[m.sup.2], and nine lean subjects were studied. The subjects participated in baseline metabolic studies consisting of an eight-hour meal tolerance test and a five-hour glucose clamp. Following completion of the baseline studies, subjects began taking 600 mg of troglitazone per day. Diabetic subjects had stopped taking all oral hypoglycemic agents two to three weeks prior to baseline. Subjects remained on the treatment for 12 weeks. At the completion of the 12-week period, repeat metabolic studies were performed. Diabetic subjects remained off of oral hypoglycemic agents and were given another five-hour glucose clamp study after two to three weeks.

Results show a significant decrease in fasting plasma glucose and a significant enhancement of insulin-stimulated glucose disposal during treatment in the diabetic subjects. A positive correlation between the change in fasting hepatic glucose output (HGO) and the change in fasting plasma glucose with troglitazone in the diabetic subjects was seen. When all therapy was discontinued for two to three weeks, neither plasma glucose nor insulin-stimulated glucose disposal showed significant change. In the obese subjects, researchers saw an improvement in insulin-stimulated glucose disposal when taking troglitazone. This resulted in maintenance of euglycemia through the lowering of plasma insulin concentrations. There was an observed increase in both glucose clearance and fasting HGO in lean subjects.

This study shows that troglitazone lowers fasting and postprandial glucose in type 2 diabetics by improving peripheral insulin sensitivity and through affecting hepatic glucose output. It appears to have insulin-sensitizing effects in obese individuals. This suggests that troglitazone may potentially be used for the primary prevention of type 2 diabetes.

J. Frias, Y. Druszynska, J. Yu, et al., Metabolic Effects of Troglitazone Therapy in Type 2 Diabetic, Obese, and Lean Normal Subjects, Diabetes Care 23:64-69 (January 2000) [Correspondence: Jerrold M. Olefsky, MD, Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla, CA 92093. E-mail: jolefsky@uscd.edu.]

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