Study Raises Concerns About Risks of Diabetes Drug
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JEFFREY BROWN: Since it first became available in 1999, Avandia has become a popular medication to help control Type 2 diabetes, used by 2 million people a year worldwide. But a study released today by the New England Journal of Medicine has raised some big questions, suggesting the drug significantly increases the risk of heart attacks and death.
Here to tell us more is Susan Dentzer of our Health Unit. The unit is a partnership with the Robert Wood Johnson Foundation.
Susan, first, tell us more about the study and what it found?
SUSAN DENTZER, NewsHour Health Correspondent: Jeff, a well-known cardiologist named Dr. Steve Nissen, who’s with the Cleveland Clinic, who is one of the people who actually raised concerns early on about the drug Vioxx, which is the pain-relieving drug that was pulled off the market in 2004, basically began to look at some results that had been published over the last year in medical journals about this drug, Avandia, which, as we said, is a large — it’s the largest oral medication used for Type 2 diabetes, which used to be called adult-onset diabetes, but now it affects so many kids and adolescents that it’s just called Type 2.
He got concerned about these results, because one of the complications of diabetes can be heart disease. And so it’s one of the things you want to prevent. These trial results that he looked at actually showed that, although the drug was effective in controlling diabetes, particularly when compared to other drugs or dummy pills, it also raised the risk of heart attacks.
He got concerned enough about this that he went to the Web site of the manufacturer of Avandia, which is GlaxoSmithKline, looked at the results of all of the trials, and put together what’s called a meta-analysis, which is a statistical way of grouping lots of studies together.
When he grouped together 42 different studies, he showed statistically that Avandia caused a 43 percent increased risk of heart attack in the patients who took it, as opposed to control groups, and a 64 percent increased risk of death. So he actually just performed this analysis several weeks ago.
JEFFREY BROWN: This all happened very quickly?
SUSAN DENTZER: Very quickly, it was speeded to the New England Journal of Medicine, a very fast peer-review process…
JEFFREY BROWN: Which also put it out very quickly, right?
SUSAN DENTZER: … put it out online, and basically in the space of less than a month, these study results are out.
Problems with class of drugs
JEFFREY BROWN: Give us a little context here about Avandia, how important it's become, and this type of drug. Have there been problems with it before?
SUSAN DENTZER: Yes. This is one of a class of drugs that is known by the acronym TZDs. It's a class of drugs that works by actually turning on or off genes that are involved in the process by which the body responds to insulin and takes up glucose, and that, of course, is the heart of diabetes.
One of the drugs, early drugs in this class, Rezulin, was actually withdrawn from the market in 2000 because it caused liver failure and death. And since Avandia was first tested before it was even approved for sale, there were so-called signals, signs that there could be some problems, specifically in patients with congestive heart failure.
Some of the symptoms were made worse. The drug seems to be linked to weight gain in diabetes patients, as well as some vision problems, so there have been concerns for a long time.
And, actually, as a result of some of those concerns, the manufacturer, GlaxoSmithKline, started a trial in 2000 to try to look at effects of this drug on large, large groups of patients. That trial result, though, won't be out until 2009. So, for the moment, this is the best indication that we have that there are problems with the drug.
Manufacturer's response to FDA
JEFFREY BROWN: And yet the company today said, put out a release that says it strongly disagrees with the conclusions. The FDA put out an alert, safety alert, but it also did not -- it said it will not do anything yet. It will not tell the company to take any further action.
SUSAN DENTZER: Not for the moment. And the company did respond, as you say, but the FDA also pointed out that GSK, the manufacturer, gave the FDA, back last fall, another meta-analysis, the same kind of study that showed similar results, a 30 percent to 40 percent increased risk of heart attack.
Now, again, GSK says it's not the right kind of study to look at. We need the results from this big, randomized, controlled trial, the results of which will not be out until 2009, before we definitively know the answer. So it says action is premature. And apparently, at this point, the FDA feels that way, also, because, as you said, what it did say was issue this alert and suggest that patients need to talk to their doctors.
JEFFREY BROWN: And that's the obvious question, and it comes up all the time in these kinds of studies. What do consumers do?
SUSAN DENTZER: At this point, the advice, again, from the FDA is talk to your physician if you're on this drug. There are other classes of medication that you could switch to.
And for people who are at high risk of heart disease or heart attack, that may be a well-founded choice. The problem is, of course, that for people with Type 2 diabetes, many of them are already at risk of these heart attacks. And so it's difficult to tease out exactly who might be at greater risk, but, at this point, the FDA says talk with your doctor about it.
A need to reform approval process?
JEFFREY BROWN: There was an editorial that accompanied this story in the New England Journal in which the authors wrote, quote, "This represents a major failure of the drug use and drug approval processes in the U.S.," again going to the old, long-running question now of the FDA approval and monitoring process.
SUSAN DENTZER: Exactly. And many people today were drawing parallels with the Vioxx story.
There's legislation now to reform the FDA working its way through Congress. And many members of Congress today, it's fair to say, just went ballistic about this. They said, once again, we have a case where we had signals, signs that there was a problem with drugs, that for various reasons the FDA did not take action.
And, in fact, that is now what Dr. Nissen wants. He wants essentially to go back to the company and say, "We want specific data involving specific patients, what happened to them in these trials, so that we can monitor that very closely and really understand if these risks are as pronounced" as his study seems to indicate that they are.
JEFFREY BROWN: All right. We'll all watch going for. Susan Dentzer, thanks again.
SUSAN DENTZER: Thanks, Jeff.