Diabetes Drug Linked to Higher Risk of Death

By RONI CARYN RABIN
26 nov 2008--Elderly people with diabetes who took the controversial drug rosiglitazone, sold under the brand name Avandia, were more likely to develop congestive heart failure and more likely to die than those receiving a similar drug called pioglitazone, sold as Actos, researchers reported on Monday.
In a surprise finding, however, patients taking rosiglitazone did not suffer more heart attacks or strokes than those taking pioglitazone, researchers said.
Rosiglitazone has been the subject of considerable controversy since 2007, when an analysis of 42 published studies concluded that the drug may dramatically increase the risk of heart attacks and other cardiovascular events, compared to various other treatments.
Researchers at Harvard Medical School used a database of Medicare beneficiaries to track 28,361 patients for up to five years. About half were treated with rosiglitazone and half were taking pioglitazone.
Death rates were 15 percent higher among patients treated with rosiglitazone, compared to those taking pioglitazone, and the incidence of congestive heart failure was 13 percent higher, the researchers found.
“Rosiglitazone was associated with greater mortality,” said Dr. Wolfgang C. Winkelmayer, assistant professor of medicine at the Harvard Medical School and first author of the study, published in The Archives of Internal Medicine.
The study published today is an observational study, and officials at GlaxoSmithKline, which manufactures rosiglitazone, dismissed the findings, saying they are inconsistent with evidence from more rigorous randomized clinical trials.
These include interim results reported from a six-year trial involving 4,447 patients, which company officials noted has found no significant increases in deaths from cardiovascular disease or other causes in patients taking rosiglitazone.
Although the current study also found no differences in heart attack and stroke rates, Dr. Winkelmayer suggested the higher death rates among patients taking rosiglitazone may be due to underlying cardiovascular disease that was never diagnosed in the elderly patients, whose average age was 78.
“In much older adults, it is possible if they do have a stroke or myocardial infarction, they might actually die immediately and never make it to the hospital for a diagnosis, so the excess cardiac events might show up as deaths,” Dr. Winkelmayer said.
Dr. John Buse, chief of endocrinology at the University of North Carolina School of Medicine and president of the American Diabetes Association, said the new study is important but limited.
“This is about the tenth report suggesting that rosiglitazone is associated with excess cardiovascular problems,” he said. “We don’t have proof yet.”
Both the American Diabetes Association and the European Association for the Study of Diabetes have removed rosiglitazone from lists of recommended treatments for type 2 diabetes.
The consumer watchdog group Public Citizen went further last month, calling on the Food and Drug Administration to ban the drug and claiming that it causes liver failure, vision impairment and other serious side effects, in addition to heart problems.
Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, said he hoped this study would be “the last nail in the coffin of this drug.”
“The big attraction of these drugs is that they are insulin-sensitizing drugs and forestall the time when someone would have to go on to insulin,” Dr. Wolfe added. “But with a 15 percent excess mortality over even pioglitazone, which itself is dangerous, that doesn’t seem like a very good tradeoff.”
A federal scientific advisory panel that reviewed rosiglitazone’s safety profile last year recommended that it remain on the market. Sales have plummeted, however.
About one million Americans still take the drug, which helps control blood sugar by increasing the body’s sensitivity to insulin, often as part of a regimen that includes other diabetes medications.