Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

Abstract

OBJECTIVESome preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes.RESEARCH DESIGN AND METHODSThis study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking.RESULTSThe group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage.CONCLUSIONSIn this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.

Trends in Antidiabetic Prescription Patterns in Japan From 2005 to 2011

“…In addition, pioglitazone was reported to be associated with an increased risk of bladder cancer. 12) There have been several reports addressing the optimal blood sugar target level, and these reports have suggested that maintaining strict blood sugar control results in a smaller risk of microvascular complications. 13,14) However, no study has shown definitively that intensive lowering of blood glucose reduces the incidence of macrovascular complications such as myocardial infarction or stroke.…”

Management of type 2 Diabetes in patients with Chronic Kidney Disease

“…Both these drugs do not accumulate in patients with CKD, but they can cause edema and heart failure (16). Hence their use is best avoided in CKD patients.…”

“…These recommendations stem from the fear generated by phenformin (the fi rst drug of this same class) induced lactic acidosis (16).…”

Rehabilitation of pioglitazone

“…4 As a result of the findings in rats, the FDA requested a 10-year study of pioglitazone in humans to assess safety with regard to bladder cancer. 5 The 8-year data have been published online 6 and the 10-year results recently were made public. 2 The main results of this study fail to show any association between pioglitazone and risk of bladder cancer.…”