Another Study Links Diabetes Drug Actos to Bladder Cancer

By Serena Gordon
HealthDay Reporter

TUESDAY, July 3 (HealthDay News) -- There's more evidence that people with type 2 diabetes may have an increased risk of bladder cancer, and taking the diabetes drug Actos may raise that risk even higher.

Taking pioglitazone (brand name Actos) raised the risk of bladder cancer by about one-fifth, according to a new analysis of previously completed studies. However, the individual risk of getting bladder cancer still remained quite low.

"The evidence suggests that this drug is associated with about a 22 percent increased risk of bladder cancer," said study senior author Jeffrey A. Johnson, the Canada Research Chair in Diabetes Health Outcomes at the University of Alberta School of Public Health, in Canada.

This isn't the first time the drug has been associated with heightened odds for bladder cancer: A study published May 31 in BMJ found that taking Actos for two years can double the risk.

Johnson said it's not clear yet how Actos might raise the risk of bladder cancer, but he said some animal studies suggested that the drug could cause crystals to form that irritate the bladder, which could potentially play a role in the development of bladder cancer.

Johnson added that it's important to keep in mind that bladder cancer is a relatively rare cancer, and even with the increased risk, any one person's risk of bladder cancer "is pretty small."

Results of the new study are published July 3 in CMAJ (the Canadian Medical Association Journal).

People with type 2 diabetes have a 40 percent increased risk of developing bladder cancer, according to background information in the current analysis. This increased risk is believed to be associated with high levels of insulin found in people with type 2 diabetes. Insulin is a hormone that helps the body turn carbohydrates from food into sugar (glucose) that can be used for fuel. Insulin is also a growth hormone, and cancer cells have insulin receptors on them, which means they can use insulin to grow, according to Johnson.

A number of studies have found that taking certain diabetes medications from a class of drugs known as thiazolidinediones appears to increase that risk even more. Actos is a thiazolidinedione, as is the drug known as Avandia (rosiglitazone). These medications are used in type 2 diabetes because they make the body more sensitive to insulin, which reduces the level of insulin the body needs. Because these drugs reduce the amount of available insulin, Johnson said he suspects the link between Actos and bladder cancer would have to be the result of a direct effect of the medication.

In the current analysis, Johnson and his colleagues reviewed the available data on thiazolidinediones and bladder cancer in type 2 diabetes. They included 10 studies in their analysis that had more than 2.6 million people. From that group, 3,643 people were newly diagnosed with bladder cancer.

Not all of the studies found a link between Actos and bladder cancer. One randomized controlled trial, which is the type of study considered the "gold standard" for such research, found no association. However, the other studies combined found a 15 percent increase in the risk of bladder cancer with the use of thiazolidinediones, which the authors attribute to the use of Actos. Overall, they found a 22 percent increased risk of bladder cancer with the use of Actos.

None of the studies in their analysis showed an association between bladder cancer and the use of Avandia. However, the use of Avandia isn't without risks. This medication has been linked to serious heart problems, and use of this drug has been restricted by the U.S. Food and Drug Administration.

"The bladder cancer risk appears to be real, but is pretty small. If you're not at risk of bladder cancer in the first place, the benefits of pioglitazone [Actos] may outweigh the potential risk," Johnson said.

Commenting on the study findings, Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City, said: "Complications of diabetes can be very bad, and some patients do very well on Actos."

He added that he sometimes uses this medication in combination with other diabetes drugs. "Bladder cancer tends to be rare, but it's much more common in men and it's also more common in smokers, so I don't put elderly male smokers on Actos. But, for other patients who have a low risk of bladder cancer, I may use Actos. We just have to be vigilant when we prescribe medications."

Zonszein said it's also important to remember that people with type 2 diabetes already have an elevated risk of bladder cancer, and they often don't start diabetes medications until they are much older, often obese and have had the disease for awhile, so "there may be a population bias" in the studies.

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SOURCES: Jeffrey A. Johnson, Ph.D., Canada Research Chair, Diabetes Health Outcomes, University of Alberta School of Public Health, Canada; Joel Zonszein, M.D., director, clinical diabetes center, Montefiore Medical Center, New York City; July 2012, CMAJ (Canadian Medical Association Journal)