Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis

He, Shiyao; Tang, Yuhong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

doi:10.1007/s13277-013-1278-x

Cited by 39 publications

(32 citation statements)

References 23 publications

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“…While TZDs are not reported to rise overall cancer risk in humans, and in several studies are even associated with lower overall cancer risk, by now, numerous studies and systematic reviews exist, pointing to a higher risk of bladder cancer for patients treated with pioglitazone. 83,85,[91][92][93][94][95][96] First, evidence was given in this regard by the prospective randomized multicentre PROactive study that was designed for cardiovascular endpoints in 5238 people with type 2 diabetes. 97 In addition, the cancer risk was increasing with the dose exposure and when applied in a long-term way.…”

Section: Insulin Sensitizers and Cancer Risk: Biguanides And Thiazolimentioning

confidence: 99%

Antihyperglycaemic therapies and cancer risk

Lutz

Staiger

Fritsche

et al. 2014

Diabetes and Vascular Disease Research

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Aims: This review is aimed at highlighting the potential mitogenic/tumour growth-promoting or antimitogenic/tumour growth-inhibiting effects of the main antihyperglycaemic drug classes. Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far. Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers. In contrast, several other drug classes may increase cancer risk. Some reason for concern remains regarding sulphonylureas and also the incretinbased therapies regarding pancreas and thyroid cancers and the sodium glucose cotransporter-2 inhibitors as well as pioglitazone regarding bladder cancer. The majority of meta-analyses suggest that there is no evidence for a causal relationship between insulin glargine and elevated cancer risk, although the studies have been controversially discussed. For α-glucosidase inhibitors and glinides, neutral or only few data upon cancer risk exist. Conclusion: Although the molecular mechanisms are not fully understood, a potential risk of mitogenicity and tumour growth promotion cannot be excluded in case of several antidiabetic drug classes. However, more large-scale, randomized, well-designed clinical studies with especially long follow-up time periods are needed to get reliable answers to these safety issues.

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Section: Insulin Sensitizers and Cancer Risk: Biguanides And Thiazolimentioning

confidence: 99%

Antihyperglycaemic therapies and cancer risk

Lutz

Staiger

Fritsche

et al. 2014

Diabetes and Vascular Disease Research

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“…As shown in Table 3, a total of six meta-analysis studies evaluating the association between the use of TZDs (specified or unspecified) and bladder cancer have been published, two in 2012 [38,66] and the other four in 2013 [65,[67][68][69]. Most of the previously mentioned clinical trials and observational studies were covered by these meta-analysis studies.…”

Section: Meta-analysis Of Clinical Trials and Observational Studiesmentioning

confidence: 99%

“…The latest published meta-analysis by He and colleagues showed an overall meta-relative risk (95% CI) of 1.50 (1.14-1.98) for pioglitazone from one RCT, five cohort studies, two case-control studies, and one drug adverse-event reporting system [69]. Dose-response analysis showed a more significant risk associated with higher cumulative dose and longer duration.…”

Section: He and Colleagues (2013)mentioning

confidence: 99%

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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“…44,45 The carcinogenic effect was also seen in an animal study 46 although the mechanism is not clarified yet. The causality is not conclusive at present 47 and several surveys are in progress.…”

Section: Pioglitazonementioning

confidence: 98%

Emerging Link between Diabetes and Cancer

Noto

Goto

Tsujimoto

et al. 2015

J of Gen and Family Med

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It has been suggested that diabetes mellitus is associated with an increased risk of cancer. Epidemiological data in Japan demonstrate that diabetes is associated with increased risk for total cancers and site‐specific cancers at colorectum, liver, and pancreas. Insulin resistance with subsequent hyperinsulinemia is the most frequently proposed hypothesis to explain this link. In addition, several facets of lifestyle including obesity, smoking, and lack of exercise, and treatment for diabetes may also affect the risk of cancer. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden, which led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. The current insights underscore the need for clinical attention and better‐designed studies of the complex interactions between diabetes and cancer.

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Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis

Cited by 39 publications

References 23 publications

Antihyperglycaemic therapies and cancer risk

Antihyperglycaemic therapies and cancer risk

A Review on Thiazolidinediones and Bladder Cancer in Human Studies

Emerging Link between Diabetes and Cancer

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