More questions are being raised about the future of diabetes drug Avandia after new research published Monday shows it puts patients at risk of serious heart problems and even death.
It's the latest development in a long and fierce debate over the safety of rosiglitazone, known by its brand name, Avandia, and comes as the U.S. Food and Drug Administration prepares to meet to discuss the issue.
Critics of the drug say the new studies provide yet more evidence that Avandia is dangerous and that it shouldn't be prescribed to patients. They also say the issue highlights serious deficiencies with federal health regulators who have so far failed to take action.
But GlaxoSmithKline Inc., which markets the drug, as well as the Canadian Diabetes Association, continue to stand by its safety and says research showing otherwise isn't definitive.
On Monday, the Journal of the American Medical Association published a study online showing Avandia is linked to higher rates of stroke, heart failure and death among older people compared to pioglitazone, a rival drug sold under the brand name Actos.
An editorial accompanying the study says the evidence demonstrates the drug needs to be taken off the market.
"Every day that we wait is a day more patients in Canada continue to receive this drug," David Juurlink, author of the editorial and head of the division of clinical pharmacology and toxicology at Toronto's Sunnybrook Health Sciences Centre, said in an interview.
At the same time, the Archives of Internal Medicine published a meta-analysis that found Avandia is associated with greater risk of heart attack and that its risks outweigh its benefits.
The two studies were made public in advance of a FDA meeting scheduled to take place next month that will examine the risks and benefits of Avandia.
Avandia and Actos are both in a class of drugs known as thiazolidinediones and have been used to treat Type 2 diabetes for about a decade. But the drugs - Avandia in particular - have come under a cloud of controversy in recent years as research began to emerge suggesting it has serious safety problems.
In 2007, a meta-analysis, which combines the findings of multiple studies, showed Avandia was associated with a 43-per-cent higher risk of heart attack and 64-per-cent higher risk of cardiovascular death compared to other treatments. Other studies performed since then have also found increased risks of cardiovascular events and death, such as a study led by Dr. Juurlink that was published in the British Medical Journal last year.
The JAMA study published this week looked at nearly 230,000 patients aged 65 or older who started taking either Avandia or Actos from July, 2006, to July, 2009. They found those on Avandia faced a 1.25-fold increased risk of heart failure compared to those on Actos, as well as a 1.27-fold increased risk of stroke and a 1.14-fold increased risk of death.
"There is no reason for a physician to prescribe Avandia to a patient with diabetes and there's no reason for a patient with diabetes to accept treatment with Avandia because safer alternatives exist," said David Graham, who led the JAMA study and is associate director for science and medicine in the Office of Surveillance and Epidemiology at the FDA.
Although he is an FDA employee, Dr. Graham readily acknowledges that his views don't reflect those of the regulatory body. He has long been calling for Avandia to be taken off the market and says the FDA's failure to do so shows the system is "broken" and favours industry over the public.
The meta-analysis published in the Archives of Internal Medicine found people on Avandia faced an estimated 28- to 39-per-cent higher risk of heart attack.
However, GlaxoSmithKline said in a statement on Monday that other studies haven't shown those problems and that Avandia is still overall safe for use.
Vincent Woo, chair of the clinical and scientific section of the Canadian Diabetes Association, said Avandia offers many benefits over other drugs, and that the association doesn't oppose its use. But he added that the association will continue to evaluate Avandia's safety and will be following developments at the FDA.
Health Canada has already said patients shouldn't take Avandia on its own, unless other alternative therapies are not appropriate.
"Health Canada will continue to review new information when it is available and take any necessary regulatory action," spokeswoman Joey Rathwell said in an e-mail Monday.