People with insulin resistance who have an ischemic stroke or transient ischemic attack and a high risk for myocardial infarction (MI) or recurrent stroke are more likely to derive benefit from pioglitazone than those at a lower risk for stroke or ischemic attack, according to a study published in JAMA Neurology.

Although pioglitazone is generally well tolerated, it is also associated with weight gain, peripheral edema, and increased risk for fracture. Therefore, it is important that clinicians consider its benefits and risks carefully for each individual patient.

In a secondary analysis of the double-blind, placebo-controlled Insulin Resistance Intervention After Stroke trial, investigators included patients who presented with a transient ischemic attack or ischemic stroke within 180 days of trial entry. There were a total of 3876 participants.

Continue Reading

The 5-year risk score for either stroke or MI was 6.0% vs 7.9% among low-risk patients taking pioglitazone vs those taking placebo, respectively (absolute risk difference, –1.9% [95% CI, –4.4%-0.6%]). In contrast, the 5-year risk score for high-risk patients receiving pioglitazone was 14.7% vs 19.6% for placebo (absolute risk difference, –4.9% [95% CI, –8.6%-1.2%]).

Patients at a high risk for stroke or MI had a slightly lower risk for pioglitazone-related weight gain and heart failure; however, the risk for bone fractures was higher in this group compared with low-risk patients (10.6% for pioglitazone vs 7.4% for placebo; [95% CI, 0.4%-6.0%]; hazard ratio, 1.40 [95% CI, 1.01-1.94]).

Related Articles

The investigators report that the size of this patient population was too small to avoid potential error during risk factor selection. In addition, the size of this patient sample may have reduced the ability to identify significant differences between hazard ratios and risk differences.

“Clinicians can use these findings to more precisely estimate the likelihood for specific absolute benefits and harms,” according to lead investigator Walter N. Kernan, MD, “allowing patients to make informed decisions based on the personal values they assign to prevention of vascular events vs risk for adverse events.”


Kernan WN, Viscoli CM, Dearborn JL, et al. Targeting pioglitazone hydrochloride therapy after stroke or transient ischemic attack according to pretreatment risk for stroke or myocardial infarction [published online September 18, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2017.2136.