A group of Montreal researchers is reporting that people with Type 2 diabetes who take the drug are more than 80 per cent more likely to develop bladder cancer than people who don't. And for those who take it over a prolonged period, the risk is higher still.
People who use the drug for more than two years have double the risk of developing bladder cancer than people who don't take the medication. And this drug — its generic name is pioglitazone — is meant to be taken over the long term.
Earlier this year Health Canada warned that there were emerging signals that pioglitazone use might be linked to elevated rates of bladder cancer. The drug regulator had done a safety assessment on the drug, looking at early data from an ongoing study being conducted by the drug's manufacturer, Takeda Canada Inc.
Based on data collected to the mid-way point of the 10-year study, Health Canada asked Takeda to update the drug's labelling to reflect the potential risk.
Dr. David Juurlink, head of the division of clinical pharmacology at the University of Toronto, said the Montreal group's findings suggest to him that the linkage is real.
"I think this is probably the single best study of this issue, and I think (it) leaves little doubt that pioglitazone is a potential risk factor for bladder cancer," said Juurlink, who was not involved in the study.
The work was done by researchers from McGill University and Montreal's Jewish General Hospital. It was published Thursday in the journal BMJ.
The scientists looked at medical records for a group of 115,727 people from Britain who started to take medication for Type 2 diabetes. Among those, 376 people developed bladder cancer and the researchers compared them to nearly 6,700 people who didn't develop the disease.
These subsets of patients were broken down into four different groups — those who had taken only pioglitazone, those who took only a sister drug, rosiglitazone (Avandia), those who had, over time, taken both and those who took neither.
The increased rate of bladder cancers was only see in the group that took pioglitazone. And the fact that the risk seemed to be greater in people who took the drug for longer or at higher dosages adds weight to the findings, Juurlink said.
Rosiglitazone or Avandia has already had its share of bad headlines. Once widely used, the drug has fallen out of favour after having been linked to increased rates of heart disease. With word of the bladder cancer concerns, use of pioglitazone has also dropped off sharply.
"For a few years now, rosiglitazone has been a highly undesirable drug. And people briefly moved to pioglitazone," Juurlink said.
"I think this study adds fuel to the argument that this is a class of drugs that people should simply not be prescribing — doctors should simply not be prescribing."
The risk identified by this study is a relative risk, in other words the risk pioglitazone users experience relative to people who didn't take the drug. Because of the way it is designed, this study cannot answer the question that is more pressing for people who took the drug: What does taking pioglitazone do to one's absolute risk of developing bladder cancer?
The study suggests, though, that the absolute risks are low. And that, Juurlink said, should be reassuring for people who used pioglitazone.
"Most people on pioglitazone are not going to end up developing bladder cancer," he said.
"But from a clinical perspective, when you have a drug that has cardiovascular toxicities and appears to increase the risk of a fairly serious cancer, one would have to argue that the drug's benefits are compelling to justify use in the face of those risks. And that's just not the case here."