This result was in contrast to an earlier 5-year interim analysis that showed a significantly higher incidence of bladder cancer in long-term pioglitazone users, according to a statement from Takeda. "The 10-year final analysis did not show any statistically significant findings of increased risk of bladder cancer with long term use of pioglitazone," the firm said.
No association with bladder cancer was seen in the 10-year data with higher cumulative doses of the drug or with longer time since initiation of therapy, Takeda said.
Other details were not released. Takeda promised that the full results would be submitted for publication and shared with regulatory authorities in the U.S., Europe, and Japan.
The 5-year study had found an increased risk among patients who took the drug for more than 2 years (HR 1.4, 95% CI 1.03-2.0). Published in Diabetes Care, it included more than 193,000 patients, 30,173 of whom had been treated with pioglitazone. There were 90 cases of bladder cancer among pioglitazone users and 791 among nonusers, and an overall nonsignificant hazard ratio of 1.2 (95% CI 0.9-1.5).
Following the publication of the interim analysis, the FDA added a warning about the risk of bladder cancer to the labeling for pioglitazone, and the drug was banned from use in France and Germany.
A different analysis published in 2012, also with about 5 years of follow-up, had confirmed an increased bladder cancer risk in pioglitazone users. And a meta-analysis of four randomized trials found an increased risk as well.
The new study was conducted by the University of Pennsylvania and Kaiser Permanente Northern California.
"The results of the study provide reassurance with regard to the use of pioglitazone and the risk of bladder cancer," said Tom Harris, who heads global regulatory affairs for Takeda, in the company statement.
Pioglitazone is a thiazolidinedione that acts as an agonist for peroxisome proliferator-activated receptor-gamma. Its use is contraindicated in patients with class III or IV heart failure.
- No association with bladder cancer was seen in the 10-year data
- Full results would be submitted for publication and shared with regulatory authorities in the U.S., Europe, and Japan
Takeda News Release, 9-2-2014