Actos Effective in Late-Stage Type 2 Diabetes
16% Lower Combined Risk of Death, Heart Attack, Stroke
Oct. 6, 2005 -- The drug Actos cuts the risk of death, heart attack, and stroke in people with advanced type 2 diabetes, a large clinical trial shows.
Actos is a new-generation diabetes drug. It lowers blood sugar levels. It also thought to lower patients' risk of heart disease, the No. 1 reason why people with diabetes tend to die far too soon.
But there's never been any direct evidence that Actos really helps prevent heart attacks or stroke. That's why John A. Dormandy, MD, University of London professor of vascular sciences, led a 19-nation study in which 5,238 patients with diabetes added either Actos or a placebo to their treatment regimen. All of these volunteers already had serious arterial disease and/or a previous heart attack or stroke.
"This study is the first evidence in a prospective clinical trial that [Actos] does decrease arterial disease in terms of heart attacks, strokes, and death," Dormandy tells WebMD. "This is the first drug for blood sugar also shown to affect heart attacks, strokes, and death."
The benefit wasn't gigantic; only a 16% lower combined risk of death from any cause, heart attack, or stroke. If 1,000 high-risk people took Actos for three years, it would prevent about 20 of these events.
Dormandy and colleagues report the findings in the Oct. 8 issue of The Lancet.
Heart Failure a Downside?
There are two major downsides to taking Actos, Dormandy says. The first is water retention and weight gain.
"These drugs are known to retain water in the body, but it varies among patients," he says. "People who take Actos are going to retain water, and some will get swelling of the ankles. On average, patients taking Actos will put on a bit of weight. That is a downside. But if that is all it is, it is better to put on weight than to have heart attack and die."
That brings up the second problem: increased heart failure in patients taking Actos.
"Is it better to have healthy arteries in the heart than a failing heart?" asks an editorial accompanying the study. Editorialist Hannele Yki-Järvinen, MD, PhD, heads the division of diabetes at the University of Helsinki, Finland.
"There was two times more heart failure in patients taking Actos," Yki-Järvinen tells WebMD. "Heart failure caused by this drug may not be as bad as heart failure in general. But we don't know how bad this is when the drug causes it."
Since patients treated with Actos were less likely to die from any cause -- and no more likely to die of heart failure than those who took a placebo -- Dormandy says this risk isn't particularly significant for most people with diabetes. And it may be that doctors overdiagnosed heart failure in Actos patients because drug-associated water gain causes swollen ankles - which may also be a symptom of heart failure.
"The crucial fact is that the number of people dying from heart failure in the two groups is identical," he says. "So even if you accept that Actos causes heart failure, it obviously isn't heart failure in any serous sense because it doesn't seem to cause death."
Since only a minority of patients develops heart failure, doctors obviously would like to avoid giving Actos to those most at risk of this apparent side effect.
"But we cannot predict who that will be," Yki-Järvinen says.