The popular diabetes medication Avandia is under scrutiny again. A new Canadian study finds that the drug, along with others like it, increases the risk of heart failure, heart attacks and death in older adults.

The study authors say their results provide further evidence that this class of medication may cause more harm than good.

The study, published in the Journal of the American Medical Association, looked at the glitazone class of drugs, which include rosiglitazone, the pharmaceutical name for Avandia and pioglitazone (sold under the name Actos). Both drugs work by increasing the body's sensitivity to insulin.

The researchers say this study is distinct from previous studies because it was not a clinical trial but the first real-world, population-based examination of the drugs.

The study examined Ontario health-care databases, looking for residents aged 65 years or older who were treated with diabetes medications and then followed them for almost four years, until March 2006.

During this time, 7.9 per cent of patients made a visit to the hospital for congestive heart failure, 7.9 per cent went to the hospital for a heart attack, and 19 per cent died. The researchers found that, compared to patients taking other diabetes medications, patients taking glitazones (Avandia & Actos) had:

  • A 60 per cent relative increase in heart failure,
  • A 40 per cent relative increase in heart attacks,
  • And a 30 per cent relative increase in death.

This translates into an estimated three additional episodes of heart failure, four additional heart attacks and five additional deaths for every 100 individuals taking these drugs, over a four-year period in the older population.

The researchers say the risk was found predominantly among those taking Avandia. They say the much small numbers of people taking Actos limited their ability to be certain about adverse events in patients taking that drug.

They also add that they cannot be sure whether similar results would be found in patients younger than 65. But lead author Dr. Lorraine Lipscombe, a researcher with the Institute for Clinical Evaluative Sciences, says her study presents a concern for older diabetic patients taking these drugs, since diabetics already have a higher risk of heart problems.

She also noted that seniors have the highest prevalence of diabetes and represent over 40 per cent of the population with the disease.

"We found that in this older group that the risks outweigh the benefits, and they should talk to their physicians about whether other alternatives should be considered," she told CTV News.

The study comes on the heels of the Food and Drug Administration in the U.S. deciding to slap a black box label warning on Avandia, telling patients that it may, or may not, increase the risk of heart attacks. It is the most severe type of warning the agency can require pending further research.

Co-author and senior ICES scientist Dr. David Alter says patients taking Avandia shouldn't panic.

"Treatment decisions must remain individualized with doctors and patients weighing the potential harms and benefits of these drugs, especially when used among the elderly who are at higher-risk of cardiac complications," he says.

Dr. Amir Hanna, deputy division head of endocrinology and metabolism at St. Michael's Hospital in Toronto and a member of the national board of the Canadian Diabetes Association, says he still believes that Avandia and other glitazones have a role to play in treating diabetes.

"We have to choose our patients well. We have to balance the pros and cons of each drug," he says.

"Older people who have underlying kidney and heart disease would not be good candidates for Avandia... For other people who are healthy, early on in the course of the disease, it is safe -- either by itself or in combination with metformin."

GlaxoSmithKline (GSK), the makers of Avandia, disagrees with the new study, saying it has "significant limitations and generates misleading conclusions." They add that larger U.S.-based studies have found "no consistent or systematic evidence that rosiglitazone increases the risk of (heart attacks) or death in comparison to other anti-diabetic agents."

GlaxoSmithKline has agreed to do a longer-term study comparing the drug to other medications, but those results won't be available for another six years.

There were 1.2 million prescriptions for Avandia issued in Canada during the past year, according to IMS Health Canada, a private company that tracks prescription drug sales.

In November, GSK issued new restrictions on the use of the drug, in consultation with Health Canada. Among the restrictions, they said it should not be taken by patients with any stage of heart failure.

The authors suggest those restrictions don't go far enough.

"Our findings argue against current labeling of (glitazones) that warns against use only in persons at high risk of (congestive heart failure), as we did not identify any subgroup of older diabetes patients who may be protected from adverse effects of (glitazones)," the authors write.

As for whether Avandia should be pulled from Canadian pharmacies, Lipscombe was not prepared to say.

"Experts from regulatory bodies such as Health Canada and the Food and Drug Administration will have to consider our findings in the context of all the evidence so far, to decide the future of these drugs," she said in a statement.

Canada AM's medical expert Dr. Marla Shapiro said it's important to remember the study was done on an older diabetic population. More information is still needed to determine the broader impact, and in particular the impact on the younger population of diabetics, she said.

For now, patients should speak to their doctors about their own personal situation.

"The bottom line is for diabetics and particularly older diabetic witness it really behooves you to have that individual conversation with your physician," she said. 

With a report from CTV medical specialist Avis Favaro and producer Elizabeth St. Philip