Pioglitazone, a drug used to treat type-2 diabetes, may prevent recurrent stroke and heart attacks in people with insulin resistance but without diabetes. The results of the Insulin Resistance Intervention After Stroke (IRIS) trial, published in the New England Journal of Medicine (NEJM), suggest a potential new method to prevent stroke and heart attack in high-risk patients who have already experienced one stroke or transient ischemic attack. The study was supported by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).
The IRIS trial was the first study to provide evidence that a drug that targets cell metabolism may prevent secondary strokes and heart attacks before diabetes develops.
“This study represents a novel approach to prevent recurrent vascular events by reversing a specific metabolic abnormality thought to increase the risk for future heart attack or stroke,” said Walter J. Koroshetz, MD, director of the NINDS.
“The IRIS trial supports the value of more research to test the vascular benefits of other interventions, such as exercise, diet, and medications, that have similar effects on metabolism as pioglitazone,” added lead author Walter N. Kernan, MD, a professor of general medicine at Yale University School of Medicine.
More than 3,000 patients from seven countries who had experienced an ischemic stroke or a transient ischemic attack within the previous six months were randomly assigned to receive pioglitazone or placebo for up to five years in addition to standard care.
Stroke or heart attack occurred in 9% of participants receiving pioglitazone and in 12% of patients given placebo, representing a relative decrease of 24%. The results suggest that 28 strokes or heart attacks may be prevented for every 1,000 patients who take pioglitazone for up to five years, according to the authors.
Insulin resistance is a hallmark of type-2 diabetes, but it also occurs in more than 50% of people with ischemic stroke who do not have diabetes. People with diabetes are known to have an increased risk of stroke. Previous research has suggested that insulin resistance increases the risk for stroke, but the IRIS trial was the first to demonstrate that insulin therapy can reduce the risk of recurrent stroke and heart attacks. Pioglitazone, however, is not FDA approved for the uses studied in the IRIS trial.
IRIS also documented a known adverse effect of pioglitazone therapy: an increased risk of bone fractures.
“More research is needed to determine the mechanisms by which pioglitazone decreases the risk for stroke and heart attack and increases the bone fracture risk, with the hope of developing strategies that maximize the benefit and minimize serious side effects in our patients,” Kernan said.