Compared with dipeptidyl-peptidase-4 inhibitors (DDP-4s) and sulfonylureas, pioglitazone was associated with an increased risk for bladder cancer. Findings from this study were published in the journal, Diabetes, Obesity and Metabolism.

Researchers used Medicare data (2007–2014) to identify patients aged 65 years and older who initiated pioglitazone (n=38,700), DPP-4s (n=82,552), or sulfonylureas (n=126,104) after at least 6 months without prescriptions for these drug classes.

Results showed that over a median of 1.2 years of treatment, 727 patients developed bladder cancer. The greatest incidence of bladder cancer was among the group who initiated pioglitazone treatment, in which there were 308 cases per 100,000 person-years. This was compared to the DPP-4 and sulfonylurea initiators who had 204 and 231 cases per 100,000 person-years; the adjusted hazard ratio (aHR) was 1.57 (1.23–2.00) and 1.32 (1.02–1.70), respectively. 

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The increased risk with pioglitazone treatment emerged within the first 2 years (aHR: 1.63 [1.22–2.17] versus DPP-4s and 1.32 [0.98–1.78] versus sulfonylureas). The researchers asserted that the findings were consistent across secondary and sensitivity analyses. The associated bladder cancer risk was also found to be reduced once pioglitazone treatment was halted.

The authors concluded that, “Pioglitazone’s relative effectiveness should be weighed against a small absolute increase in bladder cancer risk.”

In 2016, the Food and Drug Administration (FDA) issued a recommendation to clinicians not to use pioglitazone in patients with active bladder cancer and to consider the risks and benefits prior to using the drug in patients with a history of bladder cancer. 

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