People with type 2 diabetes taking Actos (pioglitazone) to control blood sugar may put themselves at risk for bladder cancer, according to a new Canadian study.

Although the absolute risk of anyone developing bladder cancer remains very low, taking the Actos pill for two years can double the risk, the researchers said.

“We believe physicians, patients and regulatory agencies should be aware of this association when assessing the overall risks and benefits of this therapy,” said lead researcher Laurent Azoulay, from the Center for Clinical Epidemiology at the Lady Davis Institute at Jewish General Hospital in Montreal.

“The association between the use of pioglitazone and bladder cancer is controversial, with several studies reporting conflicting results, from modest increased risks to no association,” said Azoulay, who also is an assistant professor in the oncology department at McGill University in Montreal.

The report was published online May 31 in the journal BMJ.

This is not the first time the drug has been linked to bladder cancer. In 2011, the U.S. Food and Drug Administration required the drug maker, Takeda Pharmaceuticals North America, to add a warning of the risk of bladder cancer to the drug’s label.

Actos’s sister drug, Avandia (rosiglitazone), has been linked to increased heart risks. Both drugs are in a class of drugs called thiazolidinediones that help control blood sugar levels in patients with type 2 diabetes. Avandia was not associated with an increased risk of bladder cancer in this study.

For this study, Azoulay’s team collected data on nearly 116,000 people treated for diabetes from 1988 to 2009 and listed in the General Practice Research Database, which contains records from more than 600 medical offices in the United Kingdom.

During almost five years of follow-up, 470 patients were diagnosed with bladder cancer. Among patients who had taken Actos, the researchers found an 83 percent increase in the relative risk for bladder cancer.

But they said the absolute risk was low — 89 cases among 100,000 people who had taken the drug at any time during the five years of follow-up. In the general U.K. population, the rate of bladder cancer among those 65 and older is 73 cases per 100,000.

The researchers also found that the risk increased as cumulative dosage increased. For those who had taken Actos for two years or longer — consuming 28,000 milligrams or more in total — the relative risk of bladder cancer was increased 88 percent to 137 cases per 100,000 patients.

Weighing the risks and benefits, doctors who treat patients disagree about the continued use of Actos.

Dr. Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York City, said “we need to be more careful with the use of this medication.”

The whole class of these drugs has come under fire, he said. “If there are more studies like this, we will not be using this medication,” he added.

Mezitis said he starts new type 2 diabetes patients on other drugs such as metformin to control blood sugar, rather than Actos. Because it’s a generic drug, metformin also is less expensive than Actos.

Mezitis also thinks more patients with type 2 diabetes will get insulin earlier instead of using drugs like Actos.

“We have to tailor treatment to each patient, and there are other ways of controlling blood sugar,” he said.

Another expert, Dr. Joel Zonszein, a professor of clinical medicine at Albert Einstein College of Medicine and an endocrinologist at the Clinical Diabetes Center at Montefiore Medical Center in New York City, said he thinks the study is weak, and the risk of bladder cancer is small.

“There is an important role for these medications,” he said. “I am probably one of the last doctors who is still supporting the use of these medications.”

Zonszein said he starts patients on Actos in combination with other drugs such as metformin to aggressively lower blood sugar. Patients, however, need to know the risks, he said.