On May 21, 2007, the New England Journal of Medicine published one study suggesting that Avandia, one of the most common type 2 diabetes medications, may increase the risk of heart attack by 43 percent. Minutes later, the panic began.
Newspapers like the Wall Street Journal, the New York Times, and the Washington Post covered the story prominently. Some articles wrongly asserted that Avandia had been proven to cause heart attacks, and U.S. News and World Report even went so far as to recommend that diabetics “suspend use” of Avandia until more research is complete.
More importantly, diabetics began to worry. Help lines and e-mail chat lists were flooded with questions. Fortunately, the Food and Drug Administration (FDA) published a response to help educate the public on the issue. Here are the FDA’s answers to some common questions:
What is this new study, and how is it different from other studies?
The article in the New England Journal of Medicine does not contain any new tests or trials. Instead, it describes a meta-analysis, also called a “pooled analysis,” of 42 different studies that had already been conducted by different researchers at different institutions.
Researchers at the Cleveland Clinic looked at these 42 studies, lumped all their findings together, and analyzed them. Their statistical analysis concluded that type 2 diabetics taking Avandia had a 43 percent greater risk of heart attack than diabetics who did not take Avandia.
But even the authors of this “pooled analysis” caution that it has “important limitations,” and that a pooled analysis “is always considered less convincing” than large, prospective drug trials. As the FDA pointed out, each of the 42 studies included was different. They were designed to study different things, such as the effect on blood glucose, or weight loss, or kidney function; none was designed to study the risk of heart attack. In some studies, participants were on Avandia alone; in others, they took Avandia in combination with insulin or metformin or other drugs. Some studies featured participants with a history of heart attacks and cardiovascular disease, while others did not. As some doctors have pointed out, lumping the studies together is not like comparing apples to apples; it is more like comparing apples to fruit salad.
Prior studies of Avandia had found no increased risk of heart attack. The two largest long-term, double-blind clinical trials, called ADOPT and DREAM, found no increased risk of heart attack from Avandia. But these studies had important limitations as well: neither was specifically designed to determine the risk of cardiovascular problems. ADOPT, published in 2006 in the New England Journal of Medicine, was designed to determine whether Avandia successfully controlled glucose levels in newly diagnosed diabetics. DREAM was designed to find out whether Avandia could delay the onset of diabetes in people who were at risk for developing the disease.
So, does Avandia cause heart attacks?
We don’t know yet. Prior studies of Avandia had found no increased risk of heart attack. The new “pooled analysis” found a significantly increased risk. In essence, the findings are in conflict. As the FDA notes, taken in this context, the risk of heart attack “remains unclear.”
Even the possibility of an increased risk, however, is cause for concern. Diabetics are already at greatly increased risk for heart attacks and other cardiovascular complications, just because of their diabetes. If one of the major medications for diabetes creates an even greater risk of heart attack, it could be disastrous. The FDA and Congress have rightly called for research to determine whether such a risk exists.
The only way to answer the question definitively is to undertake a long-term, rigorously controlled clinical trial specifically designed to determine whether Avandia increases the risk of heart attack. Fortunately, RECORD, a five-year study involving more than 4,400 participants, and specifically designed to determine the risk of heart attack, is already underway in Europe. The trial is scheduled to be completed in 2008.
Should I stop taking Avandia?
Everyone agrees that you should not stop taking a medicine without talking to your doctor. It is especially dangerous to stop treating your diabetes. Uncontrolled diabetes increases your risk for all kinds of health problems including heart disease, kidney disease, nerve problems, amputation, and blindness.
If you are taking Avandia, especially if you have a history of heart disease, you should talk to your doctor right away to determine whether to make any changes in your medication. And whatever your doctor decides, please follow his or her instructions to the letter.