According to an editorial, “by some accounts the association between pioglitazone and bladder cancer should be added to the long list of suppressed information about harm that would have affected the informed use of a drug during its patent protected life.” It notes that a substantial and fairly consistent body of evidence supports this link and this study confirms these findings. The resulting dilemma now is whether the increased likelihood of bladder cancer (which remains rare) justify withholding pioglitazone from adults with type 2 diabetes, given the benefits (stroke prevention) and potential harms (weight gain, heart failure, bone fractures) associated with its use, and the relative efficacy and safety of alternatives. Reliable evidence of comparative effectiveness and safety is needed.
In 2011, following a review by the European Medicines Agency, the MHRA had warned that use of pioglitazone is associated with a small increased risk of bladder cancer. The following new warnings and precautions for use in at-risk patients were issued:
• Patients with active bladder cancer or with a history of bladder cancer, and those with uninvestigated haematuria, should not receive pioglitazone.
• Prescribers should review the safety and efficacy of pioglitazone in individuals after 3–6 months of treatment to ensure that only patients who are deriving benefit continue to be treated. Pioglitazone should be stopped in patients who do not respond adequately to treatment (e.g. reduction in HbA1c).
• Before starting pioglitazone, the following known risk factors for development of bladder cancer should be assessed in individuals: age; current or past history of smoking; exposure to some occupational or chemotherapy agents such as cyclophosphamide; or previous irradiation of the pelvic region.
• Use in elderly patients should be considered carefully before and during treatment because the risk of bladder cancer increases with age - elderly patients should start on the lowest possible dose and be regularly monitored because of the risks of bladder cancer and heart failure associated with pioglitazone