European Medicines Agency updates on ongoing benefit-risk review of pioglitazone–containing medicines

Press release 23/06/2011

Recommendations expected in July

The European Medicines Agency is currently reviewing results from pharmacoepidemiological studies, non-clinical and clinical data and post-marketing reports on pioglitazone-containing medicines and the occurrence of bladder cancer, to assess their impact on the balance of benefits and risks of these medicines. The Committee for Medicinal Products for Human Use (CHMP) will finalise its review in July and make recommendations on the future use of these medicines.

The risk of bladder cancer in association with pioglitazone has been under close review by the Agency's CHMP since the granting of the first marketing authorisation in 2000. The marketing authorisation holder, Takeda, is conducting a number of post-authorisation studies, including a ten-year epidemiological study (Kaiser Permanente Northern California study) aimed at identifying incident malignancies associated with pioglitazone treatment in a cohort of diabetic patients. The three interim study reports have so far not confirmed a clear association between the use of pioglitazone and the occurrence of bladder cancer but there is a signal of a potential increased risk in those with longest exposure and highest cumulative dose.

The current review of pioglitazone-containing medicines was initiated on 16 March 2011 at the request of the European Commission, following an increased number of spontaneous reports of bladder cancer. The Committee considered that the accumulated evidence provided also by preclinical studies, epidemiological data and the PROactive trial (a placebo-controlled clinical trial) taken in its totality, represents a clinically relevant signal which requires further evaluation.

The CHMP discussed at its meeting on 20-24 June 2011 the results of the retrospective cohort study on pioglitazone and the occurrence of bladder cancer, carried out in France, and its potential impact on the use of these medicines across the whole EU. The Committee considered that the French study strengthened the signal of a small increased risk of bladder cancer. However, the Committee found that the study had several methodological limitations, which limit the strength of evidence provided by these epidemiological data. These data will have to be evaluated in the context of the overall available data.

The Committee agreed that at this stage there were still numerous issues that needed to be resolved before it could make recommendations on the future use of these medicines.

The CHMP has also asked its Scientific Advisory Group on Diabetes/Endocrinology (SAG-D/E) to discuss in early July 2011 the place of pioglitazone-containing medicines in the treatment of diabetes and the clinical relevance of the available data on the bladder cancer risk, and to identify risk-minimisation measures for patients in clinical practice.

The CHMP will discuss the recommendations of the SAG-D/E at its next meeting in July 2011 and give its final opinion on the benefits and risks of these medicines.

The Agency will make further announcements as soon as new information becomes available.


  • The European review of the centrally authorised pioglitazone-containing medicines Actos, Glustin, Competact, Glubrava and Tandemact and the occurrence of bladder cancer is being conducted in the context of a formal review, initiated at the request of the European Commission under Article 20 of Regulation (EC) No 726/2004, on 16 March 2011.

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