A new study is renewing the debate over a common drug for type 2 diabetes and whether it increases the risk of developing bladder cancer.

The study published today in The BMJ concludes that pioglitazone, known by the brand name Actos, is associated with an increased risk of bladder cancer for patients that use the drug, especially over a long period of time.

The drug has been the subject of numerous research projects over the years. Those studies have come up with conflicting results on pioglitazone’s connection to bladder cancer.

Officials at Takeda Pharmaceuticals, the maker of pioglitazone, said in a statement to Healthline that they are confident in the drug’s ability to help people with type 2 diabetes.

The drug has been shown in previous studies to improve glycemic levels in type 2 diabetes patients.

“We are confident in the positive benefit-to-risk profile of pioglitazone. Two large long-term observational studies found no significant increase in the risk of bladder cancer in diabetic patients taking pioglitazone,” said Elissa J. Johnsen, Takeda’s head of global product and pipeline communications.

The American Diabetes Association did not respond to Healthline’s request for comment.

Read More: Get the Facts on Diabetes »

Large Scale Study

The researchers looked at 145,000 people from the United Kingdom Clinical Practice Research Datalink who had been newly treated with antidiabetic drugs between Jan. 1, 2000 and July 31, 2013.

Those participants were followed through July 31, 2014. The mean length of time that patients were followed was 4.7 years.

During that time, 622 people were newly diagnosed with bladder cancer. Researchers calculated that pioglitazone was associated with a risk of bladder cancer at 121 incidents per 100,000 person-years.

The analysis was compared with 86 incidents per 100,000 person-years for patients using rosiglitazone, another diabetes drug in the same class as pioglitazone.

“The results of this large population-based study indicate that pioglitazone is associated with an increased risk of bladder cancer,” the study authors wrote. “The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.”

In addition, researchers said the bladder cancer risk increases with higher dosage as well as with the length of time a person takes pioglitazone.

Read More: Get the Facts on Bladder Cancer »

Years of Study

The researchers noted that pioglitazone has been the subject of a number of studies the past decade.

They highlighted a PROactive 2005 drug trial that “showed an imbalance in the number of cases of bladder cancer with pioglitazone compared with placebo.”

The findings were supported by some, but not all, research done within a few years of that study.

In 2010, the researchers noted that in a study using the Kaiser Permanente Northern California database the use of pioglitazone for more than 24 months was associated with an increased risk of bladder cancer.

However, a final analysis of that database utilizing a 10-year follow-up period concluded there was no increased bladder cancer risk with pioglitazone.

A July 2015 study published in the Journal of the American Medical Association (JAMA), and funded by Takeda Pharmaceuticals, concluded there was no link between increased bladder cancer risk and the drug.

Researchers in the latest study said additional studies with long follow-up periods are needed to fully determine whether there is an increased bladder cancer risk with the use of pioglitazone.