Study: Diabetes drug Actos doubles the risk of bladder cancer

Taking the diabetes drug pioglitazone, better known by the brand name Actos, doubles the risk of developing bladder cancer, Canadian researchers have found. In absolute terms, however, the risk remains low, the researchers found -- an extra 137 cases per 100,000 person-years. According to the National Cancer Institute, there are an estimated 70,530 cases of bladder cancer in the U.S. each year and 14,680 deaths.

The U.S. Food and Drug Administration warned in June 2011 that taking Actos for at least a year increased the risk of bladder cancer by at least 40%, and ordered the drug’s manufacturer, Takeda Pharmaceutical North America, to note the risk on the drug’s label.

Actos and its sister drug, rosiglitazone or Avandia, are members of a family of drugs known as thiazolidinediones, which have proved very effective at reducing resistance to insulin in patients with Type 2 diabetes. But concerns about the drugs have grown because they have been shown to increase the risk of cardiovascular disease. The new findings add to concerns.

A team headed by Dr. Laurent Azoulay, an epidemiologist at Jewish General Hospital in Montreal, examined data from the General Practice Database, which contains patient records from more than 600 general practices in the United Kingdom. The team studied 115,727 patients newly treated with diabetes drugs and matched each bladder cancer case to 20 healthy controls.

The team reported in BMJ, formerly known as the British Medical Journal, that 470 patients were diagnosed with bladder cancer in the average 4.6 years of follow-up, a rate of 89 cases per 100,000 person-years. The rate of bladder cancer in the general U.K. population over 65 years of age is 73 per 100,000 person-years. If patients had ever taken pioglitazone, they were at an 83% increased risk of developing bladder cancer, corresponding to a rate of 74 cases per 100,000 person-years. That increased to a rate of 88 cases for those who had taken the drug for at least two years, and 137 cases for patients who had taken a cumulative total of at least 28,000 milligrams of the drug.

The researchers found no increased risk for patients taking Avandia.

In an editorial accompanying the report, Dr. Dominique Hillaire-Buys and Dr. Jean-Luc Faillie of Le Centre Hospitalier Regional Universitaire de Montpellier in France wrote that “it can confidently be assumed that pioglitazone increases the risk of bladder cancer.” They concluded that “prescribers who are ultimately responsible for therapeutic choices can legitimately question whether the benefit-risk ratio of pioglitazone is still acceptable for their patients.”