The Food and Drug Administration warned Wednesday that the diabetes drug Actos, known generically as pioglitazone, increases the risk of bladder cancer by at least 40% when used for more than a year or in higher cumulative doses. The agency said it will require changes in the label of the drug, manufactured by Takeda Pharmaceutical North America, to reflect the new findings. The action comes as a major blow to the family of diabetes medications known as thiazolidinediones, which have proved to be very effective in reducing resistance to insulin in tissues of patients with Type 2 diabetes. Use of the only other member of the family, Avandia (rosiglitazone), has fallen sharply with evidence that the drug can increase the risk of cardiovascular disease. The FDA is not taking any further action against Actos until it receives further results from an ongoing study of the drug, but France has already suspended sales and Germany has warned physicians not to prescribe the drug to new patients.
The FDA had announced last September that it would investigate the risks of the drug, and the new warnings come as a result of that investigation. The primary source of data comes from an ongoing 10-year study of 193,099 diabetics enrolled in the Kaiser Permanente Northern California health plan. A planned 5-year interim analysis of data from that study showed that there was no overall increased risk of bladder cancer among patients who had ever received Actos. But for those who had taken the drug for more than a year, there was a 40% increased risk of the disease. That study is funded by Takeda in an effort to better understand the risks of the drug.
The agency also cited data from a study by the French National Health Insurance Plan of 1.5 million diabetics who were followed for four years. That study found a 22% increased risk of bladder cancer among patients who had ever been exposed to Actos. For those who had taken the drug for more than a year, the increased risk was 34%, while for those who had taken a cumulative dosage of more than 28,000 milligrams there was a 75% increase in risk. The risks were found primarily in men.
The agency warned physicians not to prescribe Actos to patients with active bladder cancer or those with a history of bladder cancer. Patients taking the drug and their physicians should also be alert for early warning signs of bladder cancer, which include blood in the urine, urinary urgency, pain on urination, or back or abdominal pain.
According to the National Cancer Institute, there were 70,530 new cases of bladder cancer in the United States in 2010 and 14,680 deaths.
The FDA says about 2.3 million Americans received prescriptions for Actos or related drugs between January 2010 and October of the same year. Pioglitazone is sold in combination with metformin under the brand names Actoplus Met and Actoplus Met XR and in combination with glimepiride under the name Duetact.