Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia,Pennsylvania, USA.
Diabetes care (Impact Factor: 8.42). 04/2011; 34(4):916-22. DOI: 10.2337/dc10-1068
Source: PubMed


Some 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.
This 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.
The 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.
In 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.

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Available from: Lisa Nessel, Oct 13, 2015
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    • "Overall, every use of pioglitazone was not associated with risk of bladder cancer (HR 1.2, 95% CI 0.9–1.5) [89]. Similar results, though, were obtained from a population-based cohort study (data from the French National Health Insurance Information System, the cohort included 1,491,060 diabetic patients, 155,535 of whom were exposed to pioglitazone); increased incidence of bladder cancer was associated with high cumulative doses (≥28,000 mg, HR 1.75, 95% CI 1.22–2.50, "
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    ABSTRACT: Diabetes increases cancer risk, which may be modulated by careful choice of treatment. Experimental reports showed efficacy of glitazones in various in vitro and in vivo models of carcinogenesis, but procarcinogenic effects in some models were reported too, and, similarly, data on cancer incidence in glitazone users are inconsistent. This review summarizes oncostatic effects of glitazones in preclinical and clinical studies and brings a brief summary of their impact on cancer risk in diabetic patients, with a focus on the association between pioglitazone use and bladder cancer.
    Pathology - Research and Practice 08/2014; 210(8). DOI:10.1016/j.prp.2014.06.003 · 1.40 Impact Factor
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    • "In June 2011, a French study suggested an increased risk of bladder cancer in patients who were treated with pioglitazone for more than one year leading to a temporary withdrawal of pioglitazone by the French Agency [18]. Another study in the US also indicated a possible increase in bladder cancer risk in patients on pioglitazone for more than 2 years, compared with diabetes patients who were not receiving pioglitazone [19,20]. The TGA, as well as FDA and EMA, announced safety warnings outlining a possible risk of bladder cancer related to pioglitazone use in June-July 2011; however, there have been no further updates on this issue [21-23]. "
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    ABSTRACT: A see on cardiovascular diseases and bladder cancer. The changes to the patterns of rosiglitazone and pioglitazone utilisation in Australia following the timing of these various health authority warnings such as the Australian Therapeutic Good Administration (TGA), European Medicines Agency (EMA) press releases or U.S. Food and Drug Administration (FDA) is unknown. This study investigated the utilisation patterns of rosiglitazone and pioglitazone in Australia before and after warnings of major drug authorities. We evaluated rosiglitazone and pioglitazone dispensing using the Pharmaceutical Benefit Scheme (PBS) subsidised drug dispensing data for the Australian population from February 2004 to July 2012. The World Health Organisation Anatomic Therapeutic Chemical (ATC)/Defined Daily Dose (DDD) system was used to compare the drug utilisation patterns following the announcements of EMA, FDA, and TGA safety warnings, which first occurred in May 2007. The DDD/1000population/day were examined in a series of time-series regression analysis with the drug safety warnings specified as interventions. Rosiglitazone utilisation increased steadily from 2004 until reaching a peak at 1.96/1000population/day in January 2007. Then rosiglitazone use decreased significantly after the initial EMA press release and FDA warning on cardiovascular risk in May 2007 (with a 15.04% average monthly decline, p-value <0.001), however use did not significantly decrease after the TGA warning or subsequent EMA and FDA warnings. Pioglitazone utilisation proceeded rosiglitazone in September 2008 and remained above 1.5/1000/day during 2009¿2010. However, pioglitazone utilisation has slightly declined after the FDA, EMA, and TGA warnings related to bladder cancer. Drug safety warnings were associated with a decrease in rosiglitazone and pioglitazone utilisation in Australia. Rosiglitazone began to decline prior to TGA warnings in December 2007, which suggests that Australian prescribers may have acted in response to scientific evidence or international safety warnings (EMA, FDA), prior to the response of the TGA. Minor effects were observed after bladder cancer warnings on pioglitazone utilisation.
    BMC Health Services Research 04/2014; 14(1):151. DOI:10.1186/1472-6963-14-151 · 1.71 Impact Factor
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    • "As suggested by two large observational studies, women taking TZDs have an increased risk of fractures as compared to those treated with other oral anti-diabetic drugs [147,148]. Similarly, TZDs have been associated with a questionable risk of bladder cancer [149-151]. Finally an increased prevalence of congestive hearth failure has been reported in patients on TZDs [152]. More debated remain the association between TZD use and cardiovascular events. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population.
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