Observational studies suggest a small increase in risk | References

The Therapeutic Goods Administration has warned about a possible increased risk of bladder cancer among people taking pioglitazone (Actos, Acpio, Apotex, Pizaccord, Vexazone) for more than 12 months.1 The product information (PI) and consumer medicine information (CMI) for these medicines have been, or are currently being, amended to reflect this advice.

Be aware that there may be a small increase in the risk of developing bladder cancer among people taking pioglitazone, particularly those who have been taking it long term. Advise all people taking pioglitazone to report any signs or symptoms of blood in the urine, urinary urgency, pain on urination, or back or abdominal pain.1–3 Consider other antidiabetic drugs if HbA1c levels have not fallen within 3–6 months of starting pioglitazone, as some people do not respond to glitazone therapy (see the NPS RADAR review Pioglitazone (Actos) for type 2 diabetes mellitus).2

Do not use pioglitazone in anyone with bladder cancer or a history of bladder cancer.1,2


Observational studies suggest a small increase in risk

The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study (n = 5238) reported a small non-significant increase in bladder cancer among participants taking pioglitazone (n = 14) compared with placebo (n = 6) but it was concluded that most of these cases were unlikely to be related to treatment.4

However, as a condition of continuing marketing approval, US regulators requested a long-term observational study among people with diabetes to assess the risk of bladder cancer.5 Interim results of this study showed a non-significant increase in the incidence of bladder cancer — 81.5 cases per 100,000 person years among people taking pioglitazone versus 68.8 cases per 100,000 person years among those who had never taken it (hazard ratio [HR] 1.2, 95% confidence interval [CI] 0.9 to 1.5). Among people who had taken pioglitazone for longer than 24 months the risk of developing bladder cancer was significantly higher than among those who had never taken it (HR 1.4, 95% CI 1.03 to 2.0).5

In addition, a retrospective cohort study of people with diabetes in France found a statistically significant increased risk for bladder cancer in people exposed to pioglitazone compared with people using other antidiabetic drugs (HR 1.22, 95% CI 1.05 to 1.43). People who had been taking pioglitazone for longer than 12 months had a higher risk (HR 1.34, 95% CI 1.02 to 1.75).6



  1. Therapeutic Goods Administration. Pioglitazone and risk of bladder cancer: safety advisory. Canberra: TGA, 2011. http://www.tga.gov.au/safety/alerts-medicine-pioglitazone-110718.htm (accessed 22 July 2011).
  2. European Medicines Agency. Press Release: European Medicines Agency recommends new contra-indications and warnings for pioglitazone to reduce small increased risk of bladder cancer. London: EMA, 2011. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2011/07/WC500109176.pdf (accessed 25 July 2011).
  3. Food and Drug Administration. FDA Drug Safety Communication: Update to ongoing safety review of Actos (pioglitazone) and increased risk of bladder cancer. Rockville: FDA, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm259150.htm (accessed 25 July 2011).
  4. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279\u201389. [PubMed]
  5. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011;34:916\u201322. [PubMed]
  6. Caisse National d\u2019Assurance Maladie. Risque de cancer de la vessie chez les personnes diab\u00e9tiques trait\u00e9es par pioglitazone en France: une \u00e9tude de cohorte sur les donn\u00e9es du SNIIRAM et du PMSI. Saint Denis: Afssaps, 2011.