A drug used to treat Type 2 diabetes – pioglitazone – may be effective at preventing recurrent heart attack and stroke, in patients who have some insulin resistance, but are not diabetic. Based on the results of the Insulin Resistance Intervention after Stroke (IRIS) trial, the drug may be a potential preventative option for high-risk patients who have already suffered one transient ischemic attack, or other type of stroke.
According to the researchers, the IRIS trial is the first to show that this drug could prevent additional heart attacks and strokes from occurring, before patients develop diabetes. Insulin is an important hormone in regulating blood glucose levels, and resistance to the compound occurs when the insulin produced by the body is not used correctly.
“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 Dr. Walter J. Koroshetz, director of the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS). The results of the study were published in the New England Journal of Medicine.
“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,” said Dr. Walter N. Kernan, professor of general medicine at Yale University School of Medicine, New Haven, Connecticut, and first author on the paper. Strokes occur when the cerebral blood vessels serving the brain become blocked, thereby starving the brain of oxygen and other nutrients.
The researchers studied over 3,000 individuals across seven countries who had experienced a transient ischemic attack or an ischemic stroke, within the last six months. The participants were randomized into one of two treatment groups for the trial: the first was the pioglitazone treatment group, and the second was a placebo group. Patients received one of the two treatments – along with standard care – for up to five years after the incident.
Nine percent of patients taking pioglitazone experienced an additional heart attack or stroke, compared to 11.8 percent of those patients on the placebo. The results suggest a relative decrease in the risk of recurrent heart attack or stroke of 24 percent. In addition, patients taking pioglitazone also had a 52 percent lower chance of developing diabetes.
While insulin resistance is a telltale sign of type 2 diabetes, approximately 50 percent of patients who have experienced a stroke also show insulin resistance. While previous research has shown that those with type 2 diabetes – or insulin resistance on its own – have an increased risk of stroke, the current study was the first to identify a possible treatment to prevent this.
“More research is needed to determine the mechanisms by which pioglitazone decreases risk for stroke and heart attack and increases bone fracture risk, with the hope of developing strategies that maximize benefit and minimize serious side effects in our patients,” said Kernan. Currently, pioglitazone does not have FDA-approval to be administered to those at a high risk of stroke.