Pioglitazone improves insulin sensitivity among nondiabetic patients with a recent transient ischemic attack or ischemic stroke

Background and Purpose - The aim of this study was to determine the effectiveness of pioglitazone compared with placebo for improving insulin sensitivity among nondiabetic patients with a recent transient ischemic attack (TIA) or nondisabling ischemic stroke and impaired insulin sensitivity. Methods - Eligible subjects were men and women >45 years of age who had no history of diabetes, fasting glucose <7.0 mmol/L, and impaired insulin sensitivity according to an index calculated from insulin and glucose blood levels obtained during an oral glucose tolerance test. Eligible subjects were randomized to pioglitazone 45 mg/d or placebo. After 3 months of therapy, the glucose tolerance test was repeated. Results - Between July 2000 and June 2001, we performed oral glucose tolerance tests on 75 patients with no history of diabetes, among whom 36 (50%) were found to have impaired insulin sensitivity and fasting glucose <7.0 mmol/ L. Among these 36, 20 consented to the trial. Patients assigned to pioglitazone (n = 10) and placebo ( n = 10) were similar in insulin sensitivity, age, obesity, and index event ( stroke compared with TIA), but patients assigned to pioglitazone were less likely to be male ( 4 compared with 9). The mean proportional increase in insulin sensitivity was 62% among patients assigned to pioglitazone compared with a -1% decline among patients assigned to placebo ( P = 0.0006). Mean C-reactive protein concentration declined from 0.30 to 0.20 mg/L among patients assigned to pioglitazone and increased from 0.41 to 0.45 mg/L among patients assigned to placebo ( P = 0.06 for comparison of mean change). Conclusions - Pioglitazone is effective for improving insulin sensitivity among patients with recent TIA or stroke and impaired insulin sensitivity.