TORONTO — A group of Ontario researchers is calling into question the continued use of the controversial diabetes drug Avandia, saying a competing drug in the same class is as effective and less dangerous.
The scientists, from Toronto’s Institute for Clinical Evaluative Sciences, said people taking Actos or pioglitazone for Type 2 diabetes are 23 per cent less likely to be hospitalized for heart failure and 14 per cent less likely to die than people taking Avandia or rosiglitazone.
“I can’t imagine why a patient would want to take rosiglitazone (Avandia) or a doctor would want to prescribe rosiglitazone,” principal investigator Dr. David Juurlink said in an interview.
“It’s got no advantage — not even a theoretical one — over pioglitazone (Actos). And we have this emerging or this increasing body of evidence that it’s not as safe.
“And the safety signal here is not a trivial problem. Heart failure and death — that’s a big deal.”
The research, published in the medical journal BMJ (formerly the British Medical Association Journal), looked at the anonymous records of nearly 40,000 Ontarians aged 66 and older who took one or the other of the drugs from April 1, 2002 to March 31, 2008.
Previous work had identified that Avandia, made by GlaxoSmithKline, increased the risk of heart attack of people taking it.
And it wasn’t clear whether Actos, made by Japanese drug maker Takeda, did as well. Both medications are in the same class of drugs, sometimes called the glitazones or TZDs.
Juurlink and colleagues from ICES set out to see if the cardiac safety profiles of both drugs were similar or if one was safer than the other.
They found real differences in the rates of heart failure and death among people on Avandia.
For every 120 people taking Avandia rather than Actos for a year, one more person would be hospitalized with heart failure, the authors said.
And for every 269 people who took Avandia rather than Actos for the same period, one person would die.
Juurlink said those number are not inconsequential, because these drugs are taken by millions of people.
“That sounds like sort of a smallish number.
“But when you think about the huge numbers of patients who got these drugs, we’re talking about a lot of additional harm that could be caused or perhaps was caused by rosiglitazone rather than pio(glitazone),” he said.
GSK disputed the findings, saying other studies have determined Avandia is an important treatment option for appropriate patients.
“Overall we disagree with the conclusions reached by Juurlink et al.,” the company said in an emailed response for comment on the study.
GSK noted the type of study Juurlink and his co-authors conducted — one looking back at data, called an observational study — is not considered to be as persuasive as evidence that is derived from a randomized control trial, where similar patients are randomly assigned to one treatment or the other and followed forward.
Observational studies based on anonymous medical records can’t rule out the possibility that the people taking Avandia might have been sicker, the company said.
And other factors such as whether people actually took the prescribed medication faithfully can’t be determined.
Juurlink anticipated the criticism, and had a counter argument. He said what initially seemed like a surprising finding — no difference in rates of heart attacks between patients on Avandia and those on Actos — actually supports the contention the two groups of patients were similar, healthwise.
If the patients who were prescribed Avandia were sicker than those on Actos, you would have expected to see more heart attacks in the Avandia group, he said.
Dr. Hertzel Gerstein, a diabetes expert at McMaster University in Hamilton, said he still believes there could be factors that cannot be measured that are confounding or influencing the results in ways that are unfairly detrimental to Avandia.
Gerstein and a cardiovascular expert at McMaster, Dr. Salim Yusef, are conducting a clinical trial funded by GSK comparing the outcomes of diabetes patients taking Avandia, Actos or a placebo. They will enrol 16,000 participants globally.
“The jury is out for me,” he insisted. “I don’t know, and I’m willing to say I don’t know.”
“I’m taking the approach here until we know for sure, I’m not willing to make a strong determination one way or the other.”
Dr. Steven Nissen, chair of cardiovascular medicine at the famed Cleveland Clinic, said he found the Juurlink paper persuasive.
And he said he saw little need for the GSK-funded study, the findings of which won’t be available for several years.
“I don’t understand what the value is except that it protects the company during this period of time.
By the time that that study is done, both drugs will be generically available,” he said.
Nissen was the co-author of a 2007 study review published in the New England Journal of Medicine that raised the concerns about elevated risk of heart attack among Avandia users.