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November 2017

Which Patients With Ischemic Stroke and Insulin Resistance May Benefit From Pioglitazone Hydrochloride?

Author Affiliations
  • 1Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia
  • 2Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia
JAMA Neurol. 2017;74(11):1294-1296. doi:10.1001/jamaneurol.2017.2142

The Insulin Resistance Intervention After Stroke (IRIS) trial has reported that treating insulin resistance with the peroxisome proliferator–activated receptor γ agonist pioglitazone hydrochloride reduced recurrent stroke or myocardial infarction (MI) by about one-fourth compared with placebo (pioglitazone, 9.0% vs placebo, 11.8%; hazard ratio [HR], 0.76; 95% CI, 0.62-0.93) in 3876 patients with recent (<6 months) ischemic stroke or transient ischemic attack and insulin resistance but without diabetes, heart failure, or bladder cancer.1 Pioglitazone was also associated with less incident diabetes vs placebo (3.8% vs 7.7%; HR, 0.48 [95% CI, 0.33-0.69]) but more weight gain above 4.5 kg (52.2% vs 33.7%), more peripheral edema (35.6% vs 24.9%), and more bone fracture requiring surgery or hospitalization (5.1% vs 3.2%). The weight gain reflects an increase in adipose tissue and fluid due to renal sodium retention. As the latter may predispose to heart failure, patients with a history of heart failure were excluded from the IRIS trial. Patients with a history of bladder cancer were also excluded because pioglitazone may increase the risk of bladder cancer.2-4