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Thiazolidinediones Not Linked to Bladder Cancer

Risk found unaffected by prolonged exposure to pioglitazone…

According to a recent study of more than one million people published in Diabetologia, the diabetes medications pioglitazone (Actos) and rosiglitazone (Avandia) do not appear to have an association with bladder cancer.

It is known that bladder tumors overexpress transcription factor called peroxisome proliferator-activated receptor gamma (PPAR-gamma), which is found in the lining of the urinary tract. The significance of both thiazolidinediones (TZDs), is that they act as PPAR-gamma agonists, which would be thought to have a link with bladder cancer.

Preclinical studies have shown that male rats overexposed to pioglitazone have an increased risk for bladder cancer and further studies have suggested an increased bladder cancer risk in patients taking pioglitazone. In response to the data, the withdrawal of this drug from the market in France and Germany took place. And those in the FDA and European Medicines Agency (EMA) advised against its use in people with current or previous bladder cancer.

In this study, Samira Bell, MD, of Ninewells Hospital and Medical School in the United Kingdom, and colleagues, looked at cancer and mortality data on people with type 2 diabetes from six populations worldwide. The researchers modeled the effect of cumulative drug exposure on bladder cancer incidence using data from each center, and the final amount of data was collated on 1.01 million people over 5.9 million person-years.

The final results showed no evidence of an association between cumulative exposure to pioglitazone and bladder cancer in men or women. Similarly, there was no association between rosiglitazone exposure and bladder cancer found in men (RR=1.01; 95%, CI 0.98-1.03) or women (RR=1.00; 95% CI, 0.94-1.07). Through evaluation of potential dose-response relationship, the researchers found the bladder cancer risk did not increase with longer exposure to pioglitazone.

“In summary, our large international analysis did not support a causal effect of pioglitazone on bladder cancer, thus contradicting previous studies deemed to have proven this relationship,” the researchers stated. “To fully resolve this controversy, future analyses are needed, involving longer follow-up of exposed persons and using methods to minimize allocation bias.”

Practice Pearls:

  • Bladder tumors overexpress transcription factor called peroxisome proliferator-activated receptor gamma (PPAR-gamma).
  • Thiazolidinediones act as PPAR-gamma agonists.
  • This study showed no association between cumulative exposure to pioglitazone and bladder cancer in men or women.

Levin D, Bell S, Sund R, et al. Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis. Diabetologia. 2014.