The class of diabetes drugs that includes
Avandia doesn't increase the risk of death or heart-failure hospitalizations compared with other medications, a new study says.
The report, published Monday in the
Journal of the American College of Cardiology
, adds another element to the controversy over Avandia and drugs like it, called thiazolidinediones, or TZDs.
Last month, a study published by the
New England Journal of Medicine
said people who used Avandia had a 43% greater possibility of heart attacks than people taking other diabetes medications.
article was based on compiling information from many clinical trials, and the authors admitted that such research has limitations. The cardiology journal report is based on a review of medical records of Veterans' Administration patients, and the authors concede that their work has limitations, too.
The Food and Drug Administration has convened a panel of outside medical advisers, who will meet in late July to assess the safety of TZDs. This class also includes Actos from Japan's
TZDs are called insulin sensitizers because they enable the body to better process insulin, the hormone that converts sugar into energy.
In the latest study, members of the Baylor College of Medicine in Houston and the Department of Veterans' Affairs found no statistical difference in death rates or heart-failure hospitalization rates between the users of TZDs and those who didn't use insulin-sensitizers. Heart failure is the weakening of the heart's pumping ability.
They analyzed medical records of veterans who had diabetes and heart failure and who were treated in ambulatory clinics at the VA. They followed 818 TZD patients and 4,700 other patients for two years.
The researchers didn't identify specific drugs, just a TZD group and a group that didn't use them. All patients were Type 2 diabetics, meaning they couldn't produce enough insulin or their bodies couldn't process insulin adequately.
"Contrary to previous concerns, we found no evidence for increased rates of heart-failure admission in diabetic heart-failure patients treated with TZDs," the authors say. Their research was completed before the
article was published. "Our data suggest that TZDs may be used safely in individuals with stable heart failure and that TZDs could be included in the armamentarium to adequately treat diabetes in this group."
However, the study has limitations because it was retrospective research, or a review of medical records rather than a clinical trial. "Until data from adequately powered randomized clinical trials are available ... clinicians treating individuals with diabetes and heart failure must remain cautious when using this class of medications," the researchers say.
An accompanying editorial says that until results are published for clinical trials assessing TZDs and heart failure, the latest findings "should at least keep TZDs out of the dreaded 'black box' warning for heart failure."
The editorial writers say "the cumulative beneficial effects of TZDs over time exceed their major shortcoming ... namely detectable fluid retention in less than 10% of heart failure patients." Such problems can be controlled by discontinuing the medication or by careful monitoring by heart specialists, they say. Fluid retention can lead to congestive heart failure.
Restricting or denying a drug to the 90% of patients who might benefit from TZDs because fewer than 10% have "adverse" side effects "is not shrouded in wisdom," say the editorial writers, who are cardiovascular specialists at Ohio State.
The cardiology journal says editorials don't necessarily reflect its views or those of its parent, the American College of Cardiology. Soon after the
article was published on May 21, the cardiology group joined with the American Diabetes Association and the American Heart Association to recommend doctors use caution with Avandia.
"The overall level of the risk associated with
Avandia appears to be small but nonetheless one that must be considered carefully," they said.
Glaxo has disputed the
research, and its executives have defended Avandia's safety in comments to Congress and the public. The company says Avandia's heart risks are comparable to those of other oral diabetes medications.
Still, Glaxo does say its drug increases the chance of congestive heart failure -- a more serious condition that also reduces the heart's pumping ability. It says patients with congestive heart failure shouldn't start or continue with Avandia or any TZD.
The FDA didn't order any immediate changes in the drug's label, although it did tell doctors to exercise caution. However, FDA Commissioner Dr. Andrew von Eschenbach recently said he favors adding the strictest warning label for these drugs. Takeda has already said it is working on preparing a black box for Actos.