June 9th, 2011
Pioglitazone (Actos) Suspended in France Over Cancer Concerns
Larry Husten, PHD
Sales of the popular diabetes drug pioglitazone (Actos, Takeda) have been suspended in France after a study carried out by the French health insurance fund (CNAM) found that it may increase the risk of bladder cancer. The French regulatory agency (AFSSAPS) said that new prescriptions for drugs containing pioglitazone may no longer be written, but that people who are already taking the drug may continue to do so.
Pioglitazone is the subject of an ongoing FDA safety review for a potential increased risk of bladder cancer after 2 years of exposure. The FDA has not commented on the French action. The European Medicines Agency (EMA) announced in March that it was also conducting a safety review of pioglitazone. The EMA today issued a statement about the French suspension and said that pioglitazone will be discussed at the next Committee for Medicinal Products for Human Use (CHMP) meeting on June 20-23, 2011, and that it will “recommend appropriate actions as necessary” at that time. For now, the EMA “is not recommending any changes to the use of pioglitazone-containing medicines.”
Why do we treat patients with Type 2 diabetes? to reduce events and we do not have good data that pioglitazone does reduce events. The weak data from the ProActive Trial does suggest no significant increase in CV events except for Heart failure with a NNH that is lower than the NNT to reduce non-fatal MI. When you add the significant fracture risk, the edema, weight gain and macular edema that it also causes and now the continued concern that has been there all along of bladder cancer and the high cost why would we want to consider using this agent when we have other better evidence based medications? There is no reason that Actos should;d be one of the top 10 selling medications in the world based upon this data and after 12 years it is about time to pull the plug on it like rosiglitazone.
A word on “evidence-based” medications for diabetes. Other than some obese subset UKPDS with metformin, good luck in finding quality evidence for a specific agent and CV outcomes. The heart failure issue is generally overblown with pio…no increase in HF-related death. Those with compensated class 1 or 2 have not been an issue. Meta-analysis and theoretical issues cast suspicion for the sulfonylureas, which cause weight gain. No CV outcome data with DPP-4 inhibitors or GLP analogues. Insulin causes weight gain and some preparations may be carcinogenic. Acarbose has supportingCV data but weak on glycemic control.
I agree with the limitations of ProActive…primary endpoint not meant…purists would say disregard secondary positive endpoint. macular edema: new to me. thanks.
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