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FDA finds link between pioglitazone and bladder cancer

Based on the results of interim analyses, the FDA is investigating a possible link between pioglitazone (Actos) and bladder cancer, it said in an announcement made September 17.

Actos (pioglitazone), the widely prescribed diabetes drug, is under investigation for possible associations with heightened risk of bladder cancer, U.S. health officials said Friday.

The announcement, FDA says, is based on the preliminary findings of a 10-year case-control study sponsored by manufacturer, Takeda Pharmaceutical.

While the analysis of data collected during a 5-year period from the 10-year study showed no significant association between use of pioglitazone and the heightened risk of bladder cancer, its prolonged use made diabetes mellitus patients more likely to be diagnosed with the bladder cancer, the FDA said.

"The results from two, three-year controlled clinical studies of Actos (the PROactive study and a liver safety study) demonstrated a higher percentage of bladder cancer cases in patients receiving Actos versus comparators," the FDA wrote in its safety review.

Winning its FDA approval in 1999, Actos helps improve glycemic control in adults with type 2 diabetes mellitus. It works best in combination with exercise and diet.

The study
The 10-year study (from January 1, 1997, through April 20, 2008) looked at the long-term risk for bladder cancer in roughly 193,000 patients, all with type 2 diabetes.

While the interim analysis revealed no statistically significant increase in bladder cancer among pioglitazone users, the odds of developing bladder cancer increased with increasing dose and prolonged use, reaching statistical significance after 2 years, researchers found.

The risk of bladder cancer was most significant among patients who either used pioglitazone for two or more years or those with the highest accumulative intakes of the drug, FDA found.

"The results from two, three-year controlled clinical studies of Actos (the PROactive study and a liver safety study) demonstrated a higher percentage of bladder cancer cases in patients receiving Actos versus comparators," the FDA wrote in its safety review.

Further studies warranted
More studies in this respect are required before labeling updates are considered for the drug, the FDA said.

Robert Spanheimer, Takeda's medical director for pioglitazone, highlighted the need to interpret the data “in the context of being interim results from a 10-year study."

The "investigators did a post-hoc analysis (of these preliminary data) that showed duration [of treatment] had an effect on the association," Spanheimer averred,

Until the possible risk between pioglitazone use and elevated risk of bladder cancer is established, the FDA said, the safety review announcement should not impact the clinical care and use of pioglitazone.

It further advised physicians to continue prescribing pioglitazone as per the approved marketing indications and label directions.

Also, diabetes mellitus patients taking the drug should continue doing so unless told otherwise by their physician.