Three separate studies published in the last fortnight have come out in favour of pioglitazone, demonstrating that the agent is not associated with an increase in bladder cancer risk, may protect against cardiovascular disease (CVD) and death, and may reduce the incidence of Parkinson’s disease (PD).
The first study, published in JAMA, followed 193 099 people aged 40 years or older for 10–15 years. Among these, the crude incidences of bladder cancer in pioglitazone recipients and non-recipients, respectively, were 89.8 and 75.9 per 100 000 person-years. A history of any pioglitazone use was not associated with bladder cancer (estimated hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89–1.26). However, in a separate cohort of 236 507 people who were monitored to determine the risk of 10 other cancers, a history of pioglitazone use was associated with an increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02–1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16–1.71).
In the second study, a 6-year observational cohort study published in Diabetes Research and Clinical Practice, 2864 people with type 2 diabetes and without established CVD were followed in a primary care setting. Among the 898 participants who took pioglitazone over the study period, pooled logistic regression analysis indicated a significant protective association of pioglitazone against CVD (HR, 0.54; 95% CI, 0.33–0.88) and the composite endpoint of CVD and death (HR, 0.58; 95% CI, 0.38–0.87], independently of blood glucose levels, blood pressure, lipid levels, albuminuria and renal function.
In the third study, published in PLoS Medicine, the authors matched 44 597 people who received a thiazolidinedione (TZD; including pioglitazone and the now withdrawn rosiglitazone) with 120 373 people who received any other antidiabetes drug. Between 1999 and 2013, a total of 175 TZD recipients developed PD, compared with 517 of those who received other drugs (incident rate ratio, 0.72; 95% CI, 0.60–0.87). The risk was significantly reduced in people with current TZD prescriptions but not in those with past prescriptions. As the study only included people without a PD diagnosis when they were first prescribed a TZD, it was impossible to establish whether TZD use prevents or merely slows the progression of the PD.
Pioglitazone has fallen out of favour with some clinicians, and has even been banned in some countries because of its putative association with bladder cancer. While the increased risk of prostate and pancreatic cancer merits caution, these findings suggest that pioglitazone may be one of the few oral antidiabetes drugs with evidence of a cardioprotective effect, and that the risk of bladder cancer that has led many clinicians to avoid it may in fact be absent. Regarding its effects on PD, the authors stop short of recommending it as a treatment for the disease; however, they posit that the peroxisome proliferation-activated receptor-gamma pathway, which pioglitazone acts on, may be a fruitful drug target for PD treatment.
The study on pioglitazone and cancer risk can be read in full here.
The study on pioglitazone and cardiovascular outcomes can be read in full here.
The study on TZDs and PD incidence can be read in full here.
