Data Suggest Risk of Bladder Cancer With Pioglitazone

May 19, 2011

May 18, 2011 (Bologna, Italy) — An analysis assessing the safety profile of pioglitazone (Actos, Takeda Pharmaceuticals), one of two drugs approved by the US Food and Drug Administration (FDA) in the thiazolidinedione (TZD) class, shows a consistent association between use of the diabetes medication and the risk of bladder cancer [1].

Using data from the FDA Adverse Event Reporting System (AERS), Dr Carlo Piccinni (University of Bologna, Italy) and colleagues report that 93 cases of cancer were recorded between 2004 and 2009 in patients treated with antidiabetic drugs. Of these cases, 31 patients were treated with pioglitazone, a reporting rate "indicative of a definitive risk for pioglitazone," according to the researchers.

In the analysis, the association between pioglitazone use and bladder cancer was calculated by the adverse-drug-reaction odds ratio (ROR), with investigators showing that treatment with pioglitazone was associated with a significantly increased risk of reported bladder cancers (ROR 4.30, 95% CI 2.82–6.52; p<0.001). Weaker signals of risk were also observed with gliclazide and acarbose.

As reported by heartwire in September 2010, the FDA is currently reviewing the safety of pioglitazone, citing preliminary epidemiological evidence that suggests that the diabetes medication may be linked to a higher risk of bladder cancer. The review is based on an ongoing 10-year observational cohort study as well as a nested, case-control study of the long-term risk of bladder cancer in roughly 193 000 patients with diabetes who are members of the Kaiser Permanente Northern California health plan. A preliminary analysis of these data showed an increasing risk of bladder cancer with pioglitazone exposure, a risk that reached statistical significance after 24 months.

The Italian researchers state that the "higher-than-expected reporting of bladder cancer for pioglitazone users compared with users of other antidiabetic drugs should stimulate specific case–control studies aimed at verifying the magnitude of the hazard; until the final data of the FDA investigation are available, physicians should pay careful attention to this possible risk."

The first suggestion of a possible cancer risk emerged in preclinical carcinogenicity studies described in the drug's FDA-approved label, and in two clinical trials patients taking pioglitazone had a higher rate of bladder cancer than those taking other drugs.

Speaking with heartwire about these findings, Dr Darren McGuire (University of Texas Southwestern Medical Center, Dallas, TX) said the risk of cancer has been a "smoldering concern" since 1999 and one that has lingered. That said, this paper is unable to clearly identify the exact magnitude of that risk, given that there were 31 bladder cancers for a drug that is prescribed to millions of patients. Still, clinicians need to be aware of the bladder-cancer risk and factor it into their decision-making process when selecting pioglitazone, a drug that has a relatively good cardiovascular profile, as an antidiabetic agent, said McGuire.

The authors report no conflicts of interest.

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