Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis
Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis
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DOI：
10.1007/s00125-014-3456-9
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发表时间：
2015-03-01
期刊：
影响因子：
8.2
通讯作者：
Colhoun, Helen M.
中科院分区：
文献类型：
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作者：
Levin, Daniel;Bell, Samira;Colhoun, Helen M.
关于吡格列酮使用与膀胱癌之间关系的证据是矛盾的，许多研究存在分配偏倚。本研究的目的是研究吡格列酮暴露对膀胱癌风险的影响，涉及多个国际队列。通过使用时间依赖性方法关注吡格列酮作为主要终点的累积效应，最大限度地减少了分配偏倚的可能性。2型糖尿病患者的处方、癌症和死亡率数据来自世界各地的六个人群（不列颠哥伦比亚省、芬兰、曼彻斯特、鹿特丹、苏格兰和英国临床实践研究数据链）。使用泊松回归的离散时间失效分析分别应用于每个中心的数据，以模拟累积药物暴露对膀胱癌发病率的影响，并对每次使用吡格列酮进行时间依赖性调整。然后使用固定效应和随机效应元回归将这些数据汇总。数据整理了超过590万人年的101万人。有3248例膀胱癌发生，117例暴露，中位随访时间为4.0至7.4年。总体而言，在调整了年龄、日历年、糖尿病持续时间、吸烟和任何曾经使用吡格列酮的情况后，没有证据表明男性（每100天累积暴露的比率[RR]为1.01；95% CI为0.97,1.06）或女性（RR为1.04；95% CI为0.97,1.11）累积暴露于吡格列酮和膀胱癌之间存在任何关联。罗格列酮与男性膀胱癌（RR 1.01; 95% CI 0.98, 1.03）或女性膀胱癌（RR 1.00; 95% CI 0.94, 1.07）没有关联。在这项大型多人群汇总分析中，吡格列酮或罗格列酮的累积使用与膀胱癌的发病率无关。
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.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 pioglitazone. These were then pooled using fixed and random effects meta-regression.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).The cumulative use of pioglitazone or rosiglitazone was not associated with the incidence of bladder cancer in this large, pooled multipopulation analysis.