As insulin resistance is present in more than 50% of patients without diabetes who have had an ischemic stroke or TIA, addressing this issue seems central to the treatment of these individuals. As one medication, pioglitazone, a peroxisome proliferator-activated receptor y agonist, has been found to reduce the risk of cardiovascular events in patients with type 2 diabetes, this study assessed the effect of this medication on the occurrence of stroke and myocardial infarction after ischemic stroke or transient ischemic attack (TIA).

Subjects were patients at least 40 years of age, with a stroke or TIA during the six months before randomization. Patients were included with insulin resistance, defined as a value of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. Subjects were randomized to receive either pioglitazone at 45 mg per day or a matching placebo. The participants were contacted every four months, with the last scheduled contact before July of 2015. The primary outcome measure was the first fatal or nonfatal stroke or myocardial infarction.

A total of 3，895 patients were enrolled, with a median age of 63.5 years. During a median of 4.8 years follow-up, the primary outcome of stroke or myocardial infarction occurred in nine percent of the treatment group and 11.8% of the placebo group(P＝0.007). The findings did not change after adjustment for covariates. Among secondary outcomes, the rate of progression to diabetes was lower in the treatment group than in the placebo group (P<0.001). Patients in the treatment group demonstrated more weight gain, edema, shortness of breath and bone fractures than did the placebo group.

This study of patients with a history of stroke or transient ischemic attack who were insulin resistant but not diabetic found that treatment with pioglitazone, an insulin sensitizing drug, reduced the risk of stroke or myocardial infarction, and was associated with a lower risk of developing diabetes.