Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes

Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kumiko; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

doi:10.1016/j.diabres.2012.11.013

Cited by 33 publications

(52 citation statements)

References 8 publications

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“…The authors reported a hazard ratio (95% CI) of 1. 75 [57]. A significantly higher risk was observed in 425 patients who had been taking pioglitazone for < 24 months, with an estimated hazard ratio (95% CI) of 2.73 (1.11-6.72).…”

Section: Japan: Fujimoto and Colleagues (Single Hospital-based Retrosmentioning

confidence: 90%

“…In a retrospective cohort analysis of 21,335 patients with type 2 diabetes recruited from a single Japanese hospital during a 12-year period from 2000 to 2011, Fujimoto and colleagues identified a total of 170 cases of bladder cancer in the patients with diabetes (0.8%) [57]. Among them, nine cases of bladder cancer were seen in 663 patients (1.36%) who had been taking pioglitazone.…”

Section: Japan: Fujimoto and Colleagues (Single Hospital-based Retrosmentioning

confidence: 98%

“…The major population-based cohorts used in these studies are derived from administrative databases, which include the Kaiser Permanente Northern California (KPNC) database in the United States [9,45], the US pharmacy claims database [46], the national health insurance in France (the CNAMTs study: Caisse Nationale d'Assurance Maladie des Travailleurs Salariés) [11], the Health Improvement Network (THIN) or General Practice Research Database (GPRD) in UK [47][48][49], and the National Health Insurance (NHI) reimbursement databases of Taiwan [50][51][52][53][54][55][56]. Hospital-based design was applied in a Japanese report [57] and in a Korean study [58]. A report using the Adverse Event Reporting System of the US Food and Drug Administration (FDA) [59] and a case series report from India [60] are also available.…”

Section: Observational Studiesmentioning

confidence: 99%

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A Review on Thiazolidinediones and Bladder Cancer in Human Studies

Tseng

2014

Journal of Environmental Science and Health, Part C

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There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison studies using well-designed and uniform methodology to clarify the risk in specific sexes, ethnicities, and other subgroups and to evaluate the interaction with other environmental risk factors or medications will be helpful to identify patients at risk.

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Section: Japan: Fujimoto and Colleagues (Single Hospital-based Retrosmentioning

confidence: 90%

Section: Japan: Fujimoto and Colleagues (Single Hospital-based Retrosmentioning

confidence: 98%

Section: Observational Studiesmentioning

confidence: 99%

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A Review on Thiazolidinediones and Bladder Cancer in Human Studies

Tseng

2014

Journal of Environmental Science and Health, Part C

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“…The risk of bladder cancer in case with taking pioglitazone is still controversial 38,39) . One retrospective study assessing the association between the risk of bladder cancer and use of pioglitazone in Japanese patients with type 2 diabetes showed a 1.36% (9 of 663) risk of bladder cancer and a non-significant overall increase in the risk of bladder cancer (HR, 1.75; 95% CI, 0.89 -3.45) 40) . Although the risk of bladder cancer and the use of pioglitazone in our study showed a similar trend to the previous report, a further analysis of this issue will be needed.…”

Section: Discussionmentioning

confidence: 99%

Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study

Tanaka

Yamashiro

Okuma

et al. 2015

JAT

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Aim:Prediabetes is an independent risk factor for future stroke. However, no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes. Here we investigated the effects of pioglitazone, a potent peroxisome proliferator-activated receptor-gamma agonist, for the reduction of recurrent stroke in patients with prediabetes. Methods: Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack (TIA) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test. These patients were randomized to either receive or not receive pioglitazone. The primary endpoint was a recurrence of ischemic stroke. Results: A total of 120 patients were enrolled in the study. Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone. The majority of patients (68.3%) were prescribed 15 mg of pioglitazone, while the remaining patients (31.7%) were treated with 30 mg of pioglitazone. Over a median follow-up period of 2.8 years, treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint (recurrence of stroke) than that observed in the control group [event rate 4.8% pioglitazone vs 10.5% control, hazard ratio 0.62, 95% confidence interval 0.13 -2.35, p 0.49]. However, differences were not statistically significant. Conclusions: While this study was too underpowered to determine the effect of pioglitazone, the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes. J Atheroscler Thromb, 2015; 22: 1305-1316.

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“…Since these cautions, several studies and meta-analyses of published data have reported contradictory results [12][13][14][15][16][17][18][19][20][21][22][23][24]. This may result from issues associated with observational study design, including limited sample size and a lack of attention to potential biases such as cancer ascertainment bias, immortal time bias, and the effects of diabetes duration and glycaemic control [25,26].…”

Section: Introductionmentioning

confidence: 97%

Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis

et al. 2014

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Aims/hypothesis The evidence on the association between pioglitazone use and bladder cancer is contradictory, with many studies subject to allocation bias. The aim of our study was to examine the effect of exposure to pioglitazone on bladder cancer risk internationally across several cohorts. The potential for allocation bias was minimised by focusing on the cumulative effect of pioglitazone as the primary endpoint using a time-dependent approach.Methods Prescription, cancer and mortality data from people with type 2 diabetes were obtained from six populations across the world (British Columbia, Finland, Manchester, Rotterdam, Scotland and the UK Clinical Practice Research Datalink). A discrete time failure analysis using Poisson regression was applied separately to data from each centre to model the effect of cumulative drug exposure on bladder cancer incidence, with time-dependent adjustment for ever use of Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3456-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. -014-3456-9 pioglitazone. These were then pooled using fixed and random effects meta-regression. Results Data were collated on 1.01 million persons over 5.9 million person-years. There were 3,248 cases of incident bladder cancer, with 117 exposed cases and a median follow-up duration of 4.0 to 7.4 years. Overall, there was no evidence for any association between cumulative exposure to pioglitazone and bladder cancer in men (rate ratio [RR] per 100 days of cumulative exposure, 1.01; 95% CI 0.97, 1.06) or women (RR 1.04; 95% CI 0.97, 1.11) after adjustment for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone. No association was observed between rosiglitazone and bladder cancer in men (RR 1.01; 95% CI 0.98, 1.03) or women (RR 1.00; 95% CI 0.94, 1.07). Conclusions/interpretation The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis.Diabetologia (2015) 58:493-504 DOI 10.1007/s00125

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Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes

Cited by 33 publications

References 8 publications

A Review on Thiazolidinediones and Bladder Cancer in Human Studies

A Review on Thiazolidinediones and Bladder Cancer in Human Studies

Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study

Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis

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