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降糖治疗与癌症风险。

Antihyperglycaemic therapies and cancer risk.

作者信息

Lutz Stefan Z, Staiger Harald, Fritsche Andreas, Häring Hans-Ulrich

机构信息

Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany German Centre for Diabetes Research (DZD), Tübingen, Germany.

Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany German Centre for Diabetes Research (DZD), Tübingen, Germany Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany.

出版信息

Diab Vasc Dis Res. 2014 Nov;11(6):371-89. doi: 10.1177/1479164114549553. Epub 2014 Sep 17.

Abstract

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 incretin-based 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.

摘要

目的

本综述旨在强调主要降糖药物类别潜在的促有丝分裂/肿瘤生长促进或抗有丝分裂/肿瘤生长抑制作用。

方法

我们回顾并讨论了目前评估临床实践中使用的抗糖尿病药物与迄今为止所描述的恶性肿瘤之间关联的最新研究。

结果

二甲双胍似乎是唯一一种在单药治疗以及与其他口服抗糖尿病药物或胰岛素联合使用时,对多种特定部位癌症均具有保护作用的抗糖尿病药物。相比之下,其他几类药物可能会增加癌症风险。对于磺脲类药物以及基于肠促胰岛素的疗法在胰腺癌和甲状腺癌方面,以及钠-葡萄糖协同转运蛋白2抑制剂和吡格列酮在膀胱癌方面,仍存在一些令人担忧的问题。大多数荟萃分析表明,虽然相关研究一直存在争议性讨论,但没有证据表明甘精胰岛素与癌症风险升高之间存在因果关系。对于α-葡萄糖苷酶抑制剂和格列奈类药物,关于癌症风险的数据为中性或仅有少量。

结论

尽管分子机制尚未完全了解,但对于几类抗糖尿病药物,不能排除存在促有丝分裂和促进肿瘤生长的潜在风险。然而,需要更多大规模、随机、设计良好且随访时间特别长的临床研究,以获得这些安全问题的可靠答案。

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