Actos (Pioglitazone) Linked to Bladder Cancer Part 2

Well, it's been almost 2 years since the Food & Drug Administration started looking into a link between Actos (pioglitazone) and bladder cancer.  And 12 months since the FDA stated there was evidence of said association but not as strong as the French & German government believed.  So I thought should point out a retrospective cohort study using nested case-control analysis published last week in the British Medical Journal concluding that pioglitazone is associated with an increased risk of bladder cancer.

So what are we to make of this new study?  I'll be the first to tell you that I wouldn't know a retrospective cohort study using nested case-control analysis if it bit me in the behind.  However, I can tell you that it's a statistical manipulation of observational data, which means it's good for developing hypotheses but not for demonstrating cause & effect.  For that, we need randomized, double blind, placebo controlled trials.

Nevertheless, while we can cry woulda, coulda, shoulda, in reality, we have to make due w/what we have.  In this case, the authors searched a cohort of 115,727 new users of glucose lowering medications between 1988 & 2009.  470 patients were diagnosed w/bladder cancer during this time but for analysis sake, the authors ignored the 94 patients who were diagnosed less than a year into their new drug use because bladder cancer, like all cancers, doesn't come on that quickly.

At that point, the 376 patients w/bladder cancer diagnosed after a year into their new drug use were than matched to 6,699 controls.  And presto!  Any use of pioglitazone was associated w/83% increased risk of bladder cancer.  And the longer the duration of use (especially after 24 months) and the higher the cumulative dosage (>28,000mg), the greater the risk.

While Avandia (rosiglitazone) is no longer easily available (only by restricted distribution) on the US Market, it's telling that the analysis found no link between use of this thiazolidinedione (TZD) and bladder cancer.  So rather than a class effect, we're looking at a drug-specific effect.  Likewise, the tables are turned when looking at rosiglitazone vs heart disease (positive association) as opposed to pioglitazone (no association), again suggesting drug effect, rather than class effect.

With this in mind, perhaps we should start reconsidering our use of pioglitazone.  Surely there must be safer therapeutic options for our diabetic patients?  And while all medications & supplements have the potential both to heal & to harm (double-edged sword effect), as the editorialists noted, the tide of evidence appears to be turning against pioglitazone.  Let's not be caught on the wrong side.

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