New JAMA Results on Diabetes Drug Pioglitazone As Cases Proceed

July 21, 2015

The results will not wipe out a recent $2.37 billion settlement reached in about 9000 bladder cancer claims involving the drug.

A large-scale study published today in JAMA found that that use of pioglitazone to treat type 2 diabetes mellitus (T2DM) did not significantly increase risk of bladder cancer, but it found more research was needed on the increased risk of pancreatic and prostate cancer.

The findings mean that the controversy over the blockbuster drug for Takeda, which markets the drug as Actos, will likely continue, 5 days after a California state appeals court reinstated a $6.5 million jury award in the first product liability trial over the drug, which had been thrown out 2 years ago.

Four months prior, Takeda had agreed to a class action settlement of $2.37 billion for 9000 claims involving pioglitazone, which arose after a 2012 in the British Medical Journal found that those who used the drug had an 83% increased risk of bladder cancer. Some countries banned the drug, but the United States did not, and Takeda did not recall it.

The results published yesterday involve 193,099 persons age 40 or older with T2DM. Of this group, 59,070 received a new diagnoses of T2DM between 1997 and 2002, and 34,181 received the drug; the average duration of use was 2.8 years. There were 1261 cases of incident bladder cancer reported in the group. Crude incidences of bladder cancer were 89.9 per 100,000 person years and 75.9 per 100,000 person years, respectively. Using pioglitazone at all was not associated with bladder cancer risk.

Researchers examined whether use of the drug was associated other cancers and found increased risk of prostate and pancreatic cancer, which they said merited further study to learn whether they were “causal or due to chance.”

The researchers had no explanation on why these follow-up results differed from the interim findings. “Because the methods were nearly identical, differences were not due to changes in methodology. The categories of dose and duration were updated in the final analyses to maintain balance in the size of the groups. However, results when the original categories were used were also not statistically significant.”

The authors speculated whether publicity around the first findings could have altered doctors’ prescribing behavior, but could not come up with an explanation.

Meanwhile, a special master will distribute the monies from the settlement of the class action suit, while individual cases that could bring larger awards will proceed.

Reference

Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. JAMA. 2015; 314(3):265-277.