Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Natl Cancer Inst. 2012 Sep 19;104(18):1411-21. doi: 10.1093/jnci/djs328. Epub 2012 Aug 9.
The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD.
We conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with a TZD (n = 18 459 patients) or a sulfonylurea (SU) (n = 41 396 patients) between July 1, 2000, and August 31, 2010, using The Health Improvement Network database in the United Kingdom. Incident cancers were identified for 196 708 person-years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU cohort (referent), adjusted for potential confounders. Risk associated with increasing duration of drug exposure was also examined. All statistical tests were two-sided.
We identified 60 incident bladder cancers in the TZD cohort and 137 cancers in the SU cohort. No difference in bladder cancer risk was found between the two cohorts (TZD vs SU, HR = 0.93, 95% CI = 0.68 to 1.29) in analyses that did not account for duration of exposure. However, the risk of bladder cancer was increased among patients with the longest duration of TZD vs SU therapy (≥ 5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those with the longest time since initiation of therapy (≥ 5 years since first use, HR = 2.53, 95% CI = 1.12 to 5.77). Risk of bladder cancer also increased with increasing time since initiation of pioglitazone (P (trend) < .001) and rosiglitazone (P (trend) = .006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P = .49).
Long-term TZD therapy (≥ 5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs.
噻唑烷二酮类（TZD）吡格列酮的使用可能会增加 2 型糖尿病患者患膀胱癌的风险。在这项研究中，我们评估了使用 TZD 与使用吡格列酮和另一种 TZD 罗格列酮相关的膀胱癌风险。
我们使用英国医疗改进网络数据库，对 2000 年 7 月 1 日至 2010 年 8 月 31 日期间开始使用 TZD（n = 18459 例患者）或磺酰脲类药物（SU）（n = 41396 例患者）治疗的 2 型糖尿病患者进行了回顾性队列研究。对 196708 人年的随访进行了癌症发病情况的评估。使用 Cox 比例风险回归模型，比较了 TZD 队列与 SU 队列（参照）的膀胱癌风险，调整了潜在混杂因素。还检查了与药物暴露时间增加相关的风险。所有统计检验均为双侧检验。
我们在 TZD 队列中发现了 60 例膀胱癌，在 SU 队列中发现了 137 例膀胱癌。在未考虑暴露时间的分析中，两个队列之间的膀胱癌风险没有差异（TZD 与 SU，HR = 0.93，95%CI = 0.68 至 1.29）。然而，在 TZD 与 SU 治疗时间最长（≥ 5 年）的患者中（HR = 3.25，95%CI = 1.08 至 9.71）和治疗开始后时间最长（≥ 5 年）的患者中（HR = 2.53，95%CI = 1.12 至 5.77），膀胱癌的风险增加。膀胱癌风险也随着吡格列酮（P（趋势）<.001）和罗格列酮（P（趋势）=.006）起始时间的增加而增加。比较吡格列酮与罗格列酮的使用，并未发现癌症风险存在差异（P =.49）。
2 型糖尿病患者长期（≥ 5 年）使用 TZD 治疗可能与膀胱癌风险增加有关，这种风险可能与所有 TZD 相关。
