Bladder Cancer Data Prompt Labeling Update for Pioglitazone

Patients on Diabetes Drug for Year or More at Increased Risk

June 22, 2011 05:30 pm News Staff

It was a rough spring for the class of drugs known as thiazolidinediones. Less than a month after the FDA announced it would place severe restrictions on medications containing rosiglitazone because of cardiovascular risks, the agency released new safety information June 15 linking pioglitazone to increased risks for bladder cancer.

A third drug in the class -- troglitazone, which was marketed as Rezulin -- was removed from the market in 2000 after it was linked to liver toxicity.

"I'd steer away from this class of drugs for now," Kevin Peterson, M.D., M.P.H., director of research in the department of family medicine and associate professor of family medicine at the University of Minnesota Medical School, told AAFP News Now. "This is a serious concern. We have other options with sulfonylureas, incretins and insulin that offer real promise to our patients. There are enough alternatives that can be just as effective and appear to be safer."

The FDA said in a safety announcement( that the warnings and precautions section of the label for pioglitazone-containing medicines and the patient medication guides will be revised to include information about the increased risk of bladder cancer associated with the diabetes drugs.

The safety information is based on the FDA's review of data from an interim analysis of an ongoing, 10-year epidemiological study involving nearly 200,000 patients being conducted by Takeda Pharmaceutical Co. Ltd.

Results from the first five years of the study show that there was no overall increased risk of bladder cancer with pioglitazone, but an increased risk of bladder cancer was noted among patients with the longest exposure to pioglitazone and in those exposed to the highest cumulative dose of the drug. Patients taking pioglitazone longer than one year had a 40 percent increase in risk compared to those who never used the medication, the FDA said.

Meanwhile, a retrospective cohort study of about 1.5 million patients with diabetes in France also found an increase in the risk for bladder cancer based on cumulative use.

"Most people who are on pioglitazone are on it for long periods of time," Peterson said. "It's a concern that has to be addressed."

The French Medicines Agency has suspended the use of pioglitazone-containing medicines in that country, pending a review of the benefits and risks of the medications by the European Medicines Agency(

The FDA said it will continue to evaluate data from the Takeda study as well as the French study.

Meanwhile, the agency issued the following recommendations for health care professionals:

  • do not use pioglitazone in patients with active bladder cancer;
  • use pioglitazone with caution in patients with a prior history of bladder cancer;
  • weigh the benefits of blood sugar control with pioglitazone against the unknown risks of cancer recurrence;
  • counsel patients to report any signs or symptoms of blood in the urine, urinary urgency, pain during urination, or back or abdominal pain, as these may be due to bladder cancer;
  • encourage patients to read the medication guide; and
  • report adverse events to the FDA's MedWatch program(

About 2.3 million U.S. patients filled prescriptions for pioglitazone-containing products from outpatient retail pharmacies from January 2010 to October 2010, the FDA said. The following drugs are affected by the agency's labeling changes:

  • pioglitazone, which is marketed as Actos;
  • pioglitazone in combination with metformin, which is marketed as Actoplus Met and Actoplus Met XR; and
  • pioglitazone in combination with glimepiride, which is marketed as Duetact.

Use of rosiglitazone-containing products in the United States declined from 235,500 prescriptions in January 2010 to about 119,000 patients in October 2010, the FDA said.

"I think people who are still on rosiglitazone need to be moved to another drug," Peterson said. "In the past, we would have switched people to pioglitazone. The good news is that there are other drugs that are very effective in treating diabetes."

Peterson said sulfonylureas -- such as glyburide, which is marketed as Micronase -- appear to be safe but have limitations in helping patients with diabetes maintain long-term control of their disease.

He said incretins, including oral dipeptidyl peptidase-4 inhibitors like sitagliptin, which is marketed as Januvia, and injectable glucagon-like peptide analogs and agonists such as exenatide, which is marketed as Byetta, show "great promise."

Peterson, however, said insulin remains one of the most effective therapies in treating diabetes. Advances in delivery methods and formulations in recent years have made long-acting basal insulin more convenient and less problematic, he noted.

"There's no single drug we can switch people to," Peterson said, "but we do have a lot of options. The important thing is that we work with patients to maintain glycemic control."

American Family Physician: AFP by Topic: Type 2 Diabetes
(some material available to members/paid subscribers only)

Additional Resource
CDC: Diabetes Public Health Resource(