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Analysis Suggests Use of Pioglitazone for Diabetes May Increase Risk of Prostate and Pancreatic Cancers But Not Bladder Cancer

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Key Points

  • Ever use of pioglitazone was not associated with a significantly increased risk of bladder cancer.
  • Ever use of pioglitazone was associated with an increased risk for prostate and pancreatic cancers.

Available data suggest an increased risk of bladder cancer with pioglitazone treatment for diabetes. In an analysis of Kaiser Permanente Northern California data reported in JAMA, Lewis et al found no significantly increased risk of bladder cancer in patients with diabetes ever using pioglitazone. Significant associations of ever use with prostate and pancreatic cancers were observed. No clear associations of risk for bladder or other cancers were found for time since initiation, duration, or cumulative dose of pioglitazone.

Study Details

The study involved Kaiser Permanente Northern California patients with diabetes, including a bladder cancer cohort of 193,099 patents aged ≥ 40 years from 1997 to 2002 and followed until December 2012, a case-control population including 464 case patients and 464 matched controls, and a cohort of 236,507 patients aged ≥ 40 years from 1997 to 2005 followed until June 2012 for 10 additional cancers (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma). Associations with pioglitazone use were analyzed by ever use, duration of use, cumulative dose, and time since initiation of treatment.

Bladder Cancer Risk

Among the 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration = 2.8 years, range = 0.2–13.2 years), and 1,261 (0.65%) had incident bladder cancer. The crude incidence rates of bladder cancer in pioglitazone users vs nonusers were 89.8 vs 75.9 per 100,000 person-years. The adjusted hazard ratio (HR) for use vs nonuse was 1.06 (95% confidence interval [CI] = 0.89–1.26). In the case-control analysis, 19.6% of bladder cancer cases vs 17.5% of control cases were pioglitazone users (adjusted odds ratio = 1.18, 95% CI = 0.78–1.80).

Risk of Other Cancers

In adjusted analyses, ever use of pioglitazone 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). Crude incidence rates for pioglitazone users vs nonusers were 453.3 vs 449.3 per 100,000 person-years for prostate cancer and 81.1 vs 48.4 for pancreatic cancer. No association of ever use with other cancers was observed, and no clear associations of the time from start, duration, or cumulative dose of pioglitazone were observed for bladder cancer or other cancers.

The investigators concluded: “There was no statistically significant increased risk of bladder cancer associated with pioglitazone use. However, a small increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether the observed associations are causal or due to chance, residual confounding, or reverse causality.”

Assiamira Ferrara, MD, PhD, of Kaiser Permanente Northern California, is the corresponding author of the JAMA article.

The study was funded by a grant from Takeda Development Center Americas Inc. For full disclosures of the study authors, visit jama.jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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