Study reassures about pioglitazone and bladder cancer

Last Updated: 2015-07-21

By Megan Brooks

NEW YORK (Reuters Health) - New observational data show no statistically significant link between the anti-diabetes drug pioglitazone (Actos, Takeda) and bladder cancer, although a small increase in risk can't be ruled out.

However, the data do hint at an increased risk of prostate and pancreatic cancer with pioglitazone use, although this could be due to chance, residual confounding, or reverse causality, the researchers say.

Dr. Assiamira Ferrara, from the Division of Research, Kaiser Permanente Northern California in Oakland, and colleagues described their analyses online July 21 in JAMA.

In a large cohort study, they saw 186 cases of bladder cancer among 34,181 patients who had ever taken pioglitazone and 1075 cases among 158,918 patients who had never used the drug (hazard ratio 1.06).

In a case-control analysis, among 373 individuals with bladder cancer, 91 had taken pioglitazone, and among 383 individuals without bladder cancer, 81 had a history of pioglitazone treatment. The adjusted odds ratio was 1.18.

The researchers also looked at ties between pioglitazone and 10 other cancer types in a cohort analysis of 236,507 individuals, including 38,190 who had a history of pioglitazone therapy. They found no link between pioglitazone and eight of the cancers (breast, lung, endometrial, colon, non-Hodgkin lymphoma, kidney/renal pelvis, rectal and melanoma).

Pioglitazone was associated with a small increased risk of cancer of the prostate (HR 1.13) and pancreas (HR 1.41), but the associations failed to reach statistical significance.

In email to Reuters Health, Dr. Ferrara said, "This study is the first to include a large number of diabetic patients with over four years of pioglitazone use. New data from our extended follow-up did not show an increased risk of bladder cancer with any duration of pioglitazone use. While this study cannot address risks associated with even longer latencies or durations of pioglitazone use, it does provide important reassurance to patients, clinicians, and regulators. Additional studies are needed to assess whether the observed associations with prostate cancer and pancreatic cancer were causal or due to chance, residual confounding, or reverse causality."

Dr. Ferrara added, "All diabetes medications have inherent risks and benefits, and as with all medications the needs and risks associated with each individual patient must be considered. This study will help doctors to better understand the risks of pioglitazone when choosing treatments for their patients with diabetes."

The coauthors of an editorial say these data "shed new light on the safety of pioglitazone" and reflect the "dynamic nature of many drug safety questions."

"As in this case, caution and further review are the appropriate responses to many safety signals. But when emerging available data - clinical, laboratory, observational, and even population-based studies - create a compelling picture of risk in excess of potential benefit to patients, the (Food and Drug Administration) should act to protect the public," write Dr. Joshua M. Sharfstein of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and Dr. Aaron S. Kesselheim of Brigham and Women's Hospital in Boston.

In a separate editorial, JAMA editors Drs. Phil Fontanarosa, Howard Bauchner, and Robert Golub say this analysis finding no statistically significant link between pioglitazone and bladder cancer is important due to the "prevalence of type 2 diabetes, fairly widespread use of pioglitazone, and safety concerns about this drug."

They add, "JAMA will continue to review studies evaluating the potential relationships between drugs, devices, or vaccines and adverse outcomes. Even though no observational study examining the relationship between an exposure and an outcome can definitely establish 'positive' cause-and-effect results, and no observational study can definitively prove 'negative' results, each study adds to the totality of evidence regarding the safety of drugs, devices, and vaccines. By publishing the results of these studies, JAMA will continue to provide information physicians can use in discussions with patients and regulatory bodies can use in policy decisions about the benefits and risks of various therapies."

The study was funded by a grant from Takeda Development Center Americas. Several authors have disclosed financial relationships with the company.

SOURCES: http://bit.ly/1LAvogz, http://bit.ly/1fjBzJA and http://bit.ly/1HGQyXT

JAMA 2015