FDA updates ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer

DALLAS ― The United States Food and Drug Administration (FDA) this week announced that use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer. The announcement is part of an ongoing safety review and the FDA stated that “five-year results showed that although there was no overall increased risk of bladder cancer with pioglitazone use, 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 pioglitazone.”

Pioglitazone (Actos) is in a class of blood sugar-lowering drugs called thiazolidinediones (TZDs).   Ten months ago, the FDA announced a decision to significantly restrict the use of another TZD called rosiglitazone (Avandia) intended to be used in conjunction with diet and exercise to improve glucose (blood sugar) control in type 2 diabetes patients. That decision was in response to data that suggest an increased risk of cardiovascular events, specifically an elevated risk of heart attacks in patients treated with rosiglitazone. Under the restriction, rosiglitazone is only be available to new patients if they are unable to manage their diabetes on other medications. Current users of rosiglitazone may continue to use the drug, but all patients must review statements describing the cardiovascular safety concerns associated with the drug and acknowledge they understand the risks.

That FDA decision followed a joint science advisory issued early last year by the American College of Cardiology and the American Heart Association which suggests these medications should be used only with close monitoring from healthcare providers as research into the use of TZD’s in diabetes control is ongoing.

For healthcare providers and their patients, the American Heart Association offers the following guidance on glucose-lowering medications:

  • Metformin should generally be the first choice, particularly in obese patients.  If it does not produce adequate HbA1c control, other medications may be considered, recognizing that knowledge is limited about the effect of other glucose-lowering agents on cardiovascular risk.
  • Use caution when prescribing a TZD (such as pioglitazone or rosiglitazone) for lowering glucose in patients and consider alternatives to a TZD if your patient has been on pioglitazone for 12 months..
  • Discuss with patients the potential risks of TZDs, including heart attack, stroke, or other possible problems, particularly in relation to the FDA’s current restrictions on rosiglitazone and the new safety alert regarding pioglitazone and the risk of bladder cancer.

 In addition, the FDA recommends that healthcare professionals “not use pioglitazone in patients with active bladder cancer” and to “use pioglitazone with caution in patients with a prior history of bladder cancer. The benefits of blood sugar control with pioglitazone should be weighed against the unknown risks for cancer recurrence.”

 For patients with diabetes, the American Heart Association recommends the following:

  • The cornerstone of prevention and treatment should be healthy lifestyle choices, such as not smoking, following a healthy diet and remaining physically active.
  • Because of the increased risk of heart disease and stroke, it is very important to achieve optimal control of your blood sugar, blood pressure and lipids (such as cholesterol and triglycerides) with lifestyle and medications when needed. For people with diabetes who are also at increased risk for heart disease, low-dose aspirin therapy is recommended as a reasonable way to prevent a first heart attack or stroke.
  • A focus on blood sugar control, keeping your HbA1c level below 7.0, is likely to reduce the risk of the “microvascular” complications of diabetes, such as kidney failure, painful nerve problems and decreased vision or even blindness.
  • Be sure to talk to your healthcare provider if these recommendations suggest that your medications may need to be changed.  You should not change medications on your own, as this can put you at risk of blood sugar levels rising out of control.

 For more information on lowering your risk for or living with diabetes, please visit http://www.heart.org/HEARTORG/Conditions/Diabetes/Diabetes_UCM_001091_SubHomePage.jsp.

 Additional resources:

FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer

 American Heart Association/American College of Cardiology joint science advisory, Feb. 2010