The diabetes drug pioglitazone is under investigation by drug regulatory agencies after evidence emerged that its long-term use could be linked to an increased risk of bladder cancer.
The US Food and Drugs Administration (FDA) warned that use of pioglitazone for more than one year could be associated with an increased risk of the disease, and added information about a potential risk to a section of the drug label on warnings and precautions for pioglitazone-containing medicines.
The decision to include safety information on a potential risk of bladder cancer came after an FDA review of data from a five-year interim analysis of an ongoing, 10-year epidemiological study conducted through the Kaiser Permanante healthcare system and funded by Takeda, the manufacturer of pioglitazone under its brand name, Actos.
The five-year results showed that although overall there was no significant increase in the risk of bladder cancer with pioglitazone use, an increased risk was noted among patients with the longest exposure, and in those exposed to the highest cumulative dose.
The FDA calculated that duration of therapy longer than 12 months was associated with 27.5 excess cases of bladder cancer per 100,000 person-years of follow-up, compared with never use.
US and European drug regulatory agencies are also monitoring a retrospective cohort study using data from 1.5 million patients with diabetes included in the French National Health Insurance Plan and followed up for four years.
The study – as yet unpublished and still subject to peer review – suggests an increased risk of bladder cancer with pioglitazone. The results showed that after adjusting for age, sex, and use of other anti-diabetic medications, there was a statistically significant 22% increase in the risk for bladder cancer in patients exposed to pioglitazone compared with those exposed to other anti-diabetic agents.
The results also showed a dose effect and and effect for exposures longer than one year. Based on the results of this study, France has suspended use of pioglitazone and Germany has recommended family doctors do not start pioglitazone in new patients.
Following the warning, the European Medicines Agency (EMA) also announced its Committee for Medicinal Products for Human Use ‘will now also assess the results of the French study and its potential impact on use of these medicines across the whole European Union’, with a decision expected in July following a meeting last week.
But it is stressed that until any statement is issued by the EMA GPs should not change their prescribing practice for pioglitazone. The MHRA said it was contributing to the EMA review and was awaiting any further recommendations.
A spokesperson for Takeda, said: ‘Takeda is confident in the therapeutic benefits of pioglitazone and its importance as a treatment for type 2 diabetes. We continuously monitor the safety and tolerability of all of our products and will continue to work with the EMA and other individual regulatory bodies to share and review all available data, and to determine appropriate next steps.’
Data from the NHS Information Centre shows 1.5 million prescriptions for pioglitazone were issued in England in 2010.