Impaired glucose tolerance is normalized by treatment with the thiazolidinedione troglitazone.

Abstract

The primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT). A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured. A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study. The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.