Pioglitazone: risk of bladder cancer

Use of pioglitazone is associated with a small increased risk of bladder cancer. Healthcare professionals should be aware of new warnings and precautions for use in at-risk patients

Article date: August 2011

Pioglitazone (Actos▼) is an oral treatment for type 2 diabetes, either on its own or combined with other oral antidiabetic agents or insulin. It is also available as a combination tablet with metformin (Competact▼).

Risk of bladder cancer

The potential risk of bladder cancer with pioglitazone was first identified at the time of licensing, observed in male rats in an animal toxicity study that supported the initial licence application. There was no evidence of a similar risk in humans at that time. The marketing authorisation (licence) holder committed to investigate the risk further in animal studies and observational studies in human use. The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has reviewed the results of these studies and other relevant data regularly. After an increase in healthcare-professional reports of bladder cancer suspected to be associated with pioglitazone, in March 2011 the EMA initiated a further European-wide review to investigate this safety signal.

Outcome of European review

The review found a small increased risk of bladder cancer in patients taking pioglitazone; however, the benefits continue to outweigh the risks for those who respond to treatment and in whom there are no identified risk factors for bladder cancer. Observational studies report relative risks ranging from 1.12 to 1.33 when diabetic patients receiving pioglitazone are compared with diabetic patients receiving other antidiabetic medicines but not exposed to pioglitazone. The increase in absolute risk is therefore likely to be small. Whether the increased risk occurs early in treatment or only after prolonged exposure remains unclear. CHMP stated that the small increased risk could be reduced by appropriate patient selection.

Advice for healthcare professionals:

  • 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 (eg, reduction in glycosylated haemoglobin, 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

Call for reporting of suspected adverse reactions

Please report suspected adverse reactions through the Yellow Card Scheme at www.yellowcard.gov.uk. When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, and treatment dates.

Further information

MHRA statement on pioglitazone

European Medicines Agency statement on pioglitazone

BNF treatment summary for type 2 diabetes

Article citation: Drug Safety Update vol 5 issue 1, Aug 2011: A1.

Post-publication note:

In March 2022, links were updated during routine review.

Published 11 December 2014