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Topics in Evidence-Based Pharmacy Practice
6/28/2012: The Risk of Bladder Cancer Associated with Pioglitazone (Actos®)
Bryan Zobeck
University of Iowa College of Pharmacy
Excerpt:"Type 2 diabetes affects approximately 26 million Americans, with nearly 2 million newly diagnosed patients annually.1 In addition to contributing to cardiovascular morbidity and mortality, diabetes is the leading cause of kidney failure and dialysis, non-traumatic lower limb amputation, and new-onset blindness in the United States.1 Pioglitazone (Actos®), FDA approved for the treatment of type 2 diabetes, exhibits its action through activation of peroxisome proliferator-activated receptor-gamma (PPAR-γ). PPAR-γ activation increases insulin-dependent glucose disposal and decreases hepatic glucose output by decreasing insulin resistance in peripheral tissues and the liver.2 PPAR-γ is also involved in angiogenesis, which is essential for solid tumor growth. PPAR-γ up-regulates vascular endothelial growth factor (VEGF) in two human bladder cancer cell lines, promoting angiogenesis and tumor growth in vitro.3 In vitro data is supported by animal studies reporting higher incidence of bladder cancer in rats receiving pioglitazone doses equivalent to 45 mg daily in humans.2,4 In addition, pioglitazone has recently been associated with increased risk of bladder..."
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