JNCI：糖尿病药物TZDs增加罹患膀胱癌风险

一个流行病学研究证实糖尿病药物或许会增加患者罹患膀胱癌的风险，根据一项发表在Journal of the National Cancer Institute杂志上的新研究证实。宾夕法尼亚大学医学院的研究人员发现，高达20％的美国糖尿病患者服用糖尿病药物噻唑烷二酮类（TZDs），这些人比那些服用磺酰脲类药物的患者来说，罹患膀胱癌的风险增高了两到三倍左右。

这项新研究从美国Health Improvement Network (THIN)数据库分析了60,000例2型糖尿病患者。他们发现，与那些服用磺酰脲类药物的患者相比，服用TZD药物吡格列酮或罗格列酮五年或五年以上的患者罹患膀胱癌的风险增加两到三倍。

长时间服TZDs的患者当中，每10万人中有170患者会罹患膀胱癌。 而服用磺脲类药物的患者中，每100,000人中有60名患者可能罹患膀胱癌。 糖尿病是最常见的全球慢性疾病之一，影响到2.85亿人。有许多因素影响该疾病的发病发展，临床医生必须权衡决定哪种药物来控制病人的糖尿病。

研究表明，糖尿病患者的医生应该非常清楚任何与膀胱癌相关的症状，并采取措施以进一步评估这些问题。虽然在美国，大多数患者不再服用罗格列酮，因为其具有严重的心血管问题，罗格列酮是最常用的处方，每年约有15万处方中含有此药物。该药物是2型糖尿病患者服用治疗糖尿病的第一线药物二甲双胍不起作用时一种常见的选择。

基于以前的数据，FDA已经警告应及时检查患者服用罗格列酮与罹患膀胱癌之间的安全风险，在法国和德国市场已不再销售此类药物。

编译自：Diabetes drugs taken by over 15 million Americans raises risk of bladder cancer

doi:10.1093/jnci/djs328
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Association Between Longer Therapy With Thiazolidinediones and Risk of Bladder Cancer: A Cohort Study

Ronac Mamtani, Kevin Haynes, Warren B. Bilker, David J. Vaughn, Brian L. Strom, Karen Glanz and James D. Lewis

Background 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.

Methods 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.

Results 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).

Conclusion 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.