Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting.

OBJECTIVE: To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications.

RESEARCH DESIGN AND METHODS: Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR).

RESULTS: Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82-6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively).

CONCLUSIONS: In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.