People with prediabetes who took the drug had a 72% reduction in diabetes risk, compared to patients who did not take it, researchers report.
They estimate that one case of diabetes could be prevented if 18 high-risk people were treated with the drug for a year.
The study appears in the March 24 issue of The New England Journal of Medicine.
The findings suggest that millions of people at high risk for diabetes may benefit from taking Actos, but experts urge caution.
Actos (pioglitazone) is in the same drug class as the controversial diabetes drug Avandia. The FDA severely restricted Avandia’s use last fall due to concerns that its use may be associated with an increase in heart attack risk.
Similar concerns have not been raised about Actos, and there are even suggestions that the drug protects the heart. But its use has been linked to fractures related to bone loss, weight gain, fluid retention, and other side effects.
Lifestyle Changes vs. Drug Treatment
American Diabetes Association vice president for medical affairs Sue Kirkman, MD, says patients at risk for type 2 diabetes should first be encouraged to make lifestyle changes before considering any drug treatment.
“Anytime we talk about long-term drug treatment for prevention, we have to have a very high reassurance that these treatments are both safe and effective,” she says.
Close to 79 million people in the U.S. have prediabetes, meaning that their blood sugar is higher than normal but not yet high enough to be considered diabetes.
Half the study participants were randomly assigned to be treated with Actos; the other half got a placebo. The patients were followed for an average of 2.4 years.
Over the course of the study, the yearly progression to diabetes was 2% in the Actos-treated patients and 7.6% in the placebo group.
About half the patients who took the insulin-sensitizing drug (48%) saw their blood sugar levels return to normal during treatment, compared to just over one-fourth (28%) of the placebo-treated patients.
Actos-treated patients also had reductions in diastolic blood pressure and increases in HDL “good” cholesterol. Treatment with the diabetes drug was also associated with a 31% decrease in the rate of carotid artery thickening.
But the active treatment was also associated with significantly greater weight gain (8 and 1/2 pounds compared to 1 and 1/2 pounds). And fluid retention was twice as common in the Actos patients (13% vs. 6.4%).
Funding for the study was provided by Actos manufacturer Takeda Pharmaceuticals.
Weighing Risks vs. Benefits
Study co-researcher Robert R. Henry, MD, says the findings show that targeting insulin sensitivity can have a dramatic impact on diabetes risk.
The treatment-related reduction in diabetes risk was higher than that associated with healthy changes in lifestyle in a diabetes prevention study from the National Institutes of Health.
But Henry says lifestyle intervention will remain the recommended treatment for most of his patients with prediabetes. Henry is chief of endocrinology and diabetes at the VA San Diego Healthcare System and the president of medicine and science with the American Diabetes Association.
“I might consider pioglitazone in patients who have a very high diabetes risk, but this would be a very restricted population,” he says. “As with all drug treatments, the risks and benefits have to be weighed.”