膀胱癌有利文.doc

Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting Carlo Piccinni, PHD , Domenico Motola, PHD Diabetes Care June 2011 vol. 34 no. 6 1369-1371 Abstract 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 issueneeds constant epidemiologic surveillance and urgent definition by more specific studies. A link between pioglitazone and bladder cancer first appeared in preclinical studies and was first reported on the U.S. pioglitazone label in 1999, but experimental studies recently suggested that it might be a rat-specific phenomenon (1). In the large PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study, 14 bladder cancers occurred in the pioglitazone arm (0.5%) versus 6 in the placebo arm (0.2%) (2,3), and in September 2010, the U.S. Food and Drug Administration (FDA) announced an ongoing investigation on the possible risk in humans (4). Accordingly, the drug manufacturer is conducting a 10-year observational study to address the long-term risk of bladder c