School of Public Health researcher Jeff Johnson, along with master-of-science student Isabelle Colmers, set out to verify whether this is the case and to determine the implications for diabetes treatments.
Thiazolidinediones, a class of diabetes medications, are used to help patients with type 2 diabetes lower their blood sugar by improving insulin sensitivity, and were previously thought to possibly reduce the risk of cancer. Through a systematic review and meta-analysis of published and unpublished studies involving 2.6 million patients, Colmers and Johnson confirmed that the use of pioglitazone, a type of thiazolidinedione, was associated with a 22-per-cent increased risk of developing bladder cancer.
In this research, recently published in the Canadian Medical Association Journal, Colmers and Johnson also looked at the risk associated with using rosiglitazone, another type of thiazolidinedione. Surprisingly, they found no association between rosiglitazone and bladder cancer.
"Pioglitazone and rosiglitazone work the same way when treating diabetes, so if the risk is only there with one, there's something different about that drug," says Johnson. "And it's also interesting to note that the increased risk with pioglitazone is really only seen in men."
Although the risk of cancer is certainly a factor when considering treatment options, Johnson is quick to point out that the use of thiazolidinediones as a treatment has declined over the past few years because of other associated risks.
"The absolute risk of bladder cancer associated with pioglitazone was small, and there are still many other adverse effects to consider," Johnson says. "They're associated with fractures, fluid retention, weight gain and heart failure. Rosiglitazone is also associated with increased risk of heart attacks."
"It requires balance�you want to lower the blood sugar in people with diabetes, but if you're causing all of these other problems, the risks aren't worth the benefits. The importance of our research is that it can assist physicians in making better decisions about when to use pioglitazone. "
When research first surfaced to indicate the increased risk of bladder cancer, France removed pioglitazone from the market entirely. Health Canada included warnings on drug packaging to acknowledge the risk. According to Johnson, this less extreme response is in the best interest of the patient.
"While cancer is absolutely a scary thing, there are other risk factors, such as being male, smoking and a prior history of bladder cancer. Removing pioglitazone from the market eliminates a physician's ability to use it to treat women who don't smoke, for example."
When asked about other treatment options that can replace pioglitazone, Johnson lists some alternatives that can help avoid these treatments altogether.
"If nothing else, knowing more about cancer risk may help to reinforce the importance of lifestyle modifications. You can reduce your risk of diabetes, cancer and all those chronic diseases by making healthy lifestyle choices, by not smoking, being physically active and having a healthy diet."
"That's the most important message if we want to continue to protect and promote public health."
This research was conducted by Isabelle N. Colmers BScH, Samantha L. Bowker PhD, Sumit R. Majumdar MD and Jeffrey A. Johnson PhD, and supported by the Canadian Institutes of Health Research.