VIENNA (EGMN) – The glucose-lowering drug metformin is increasingly showing an anticancer effect.
The data come from studies being conducted in both the diabetes and oncology research communities, according to experts who spoke at the annual meeting of the European Association for the Study of Diabetes.
The positive metformin story has been somewhat buried within the much broader and very complicated relationship between diabetes treatments and cancer. The subject first caught the medical community’s and the general public’s attention in June, with the publication of a series of articles on the putative association between insulin glargine and cancer in EASD’s journal Diabetologia.
Much of the focus has been on the question of whether glargine or other insulin analogues could accelerate the growth of cancers in people with a predisposition to the disease. At the meeting, representatives from Sanofi-Aventis, the manufacturer of insulin glargine (Lantus), and Novo-Nordisk, maker of detemir (Levemir), presented data showing that there is no statistically significant relationship between their respective products and cancer.
But evidence for a protective effect of metformin did appear in one of the Diabetologia studies that caused the furor. Craig J. Currie, Ph.D., of Cardiff (Wales) University, and his associates found the lowest risk for cancer among users of metformin compared with other diabetes treatments, and that adding metformin to insulin reduced the progression to cancer compared with insulin treatment alone, with a hazard ratio of 0.54 in a retrospective cohort study of more than 62,809 diabetes patients.
Several lines of investigation are now looking at metformin as a potential anticancer treatment outside of diabetes, said Dr. Edwin Gale, editor-in-chief of Diabetologia. “This is an area that’s going to grow,” he commented.
The study out of Cardiff University showed that diabetes patients on insulin or insulin secretagogues were more likely to develop solid cancers than were those on metformin, while the combination with metformin abolished most of this excess risk. Metformin use was associated with lower risks of colon or pancreas cancer, but did not affect the risk of breast or prostate cancer. Use of insulin analogues was not associated with increased cancer risk as compared with human insulin (Diabetologia 2009;52:1766-77).
Similarly, in another study, metformin use was associated with reduced risk, and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetes patients (Gastroenterology 2009;137:482-8).
Dr. Currie, who also spoke at the meeting, summarized new data from an observational U.K. study from a general practice population of more than 31,421 patients on metformin monotherapy, 5,035 on insulin plus metformin, and 4,829 on insulin only. After adjustment, there was a strong dose-response relationship between insulin use and cancer, but the risk appeared to be attenuated with the addition of metformin.
Dr. Ulf Smith, president of the EASD, said that two just-published studies provide further support for the suggestion that metformin may have a protective effect against cancer. One showed a better response rate to chemotherapy among diabetic patients with breast cancer who were taking metformin (J. Clin. Oncol. 2009;27:3297-302).
The other study, published online, provides further support for the so-called “cancer stem cell” hypothesis, which suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor and thereby cause relapse of the disease. Drugs that selectively target cancer stem cells offer promise for cancer treatment, particularly in combination with chemotherapy.
In the study, conducted on mice, metformin was found to inhibit cellular transformation and selectively kill cancer stem cells in four genetically different types of breast cancer, and the combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, killed both cancer stem cells and non-stem cancer cells in culture. Thus, the combination of metformin and chemotherapeutic drugs might improve treatment of patients with breast and other types of cancers (Cancer Res. 2009 Sept. 14 [doi: 10.1158/0008-5472.CAN-09-2994]).
“The story with metformin is extremely exciting,” said Dr. Smith of the Salgrenska Center for Cardiovascular and Metabolic Research, Gotenburg, Sweden.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
维也纳（EGMN）——降糖药二甲双胍愈加表现出抗癌效应。
在今年的欧洲糖尿病研究协会（EASD）年会上，有专家报告称，上述结论是基于糖尿病和肿瘤学研究领域开展的研究数据。
由于人们历来都将注意力放在糖尿病治疗与癌症之间非常复杂的广泛联系上，因而多少有些忽略二甲双胍的这一作用。直到今年6月，EASD所属期刊《糖尿病学》（Diabetologia）刊载的一系列文章提示了甘精胰岛素与癌症之间的潜在关联，医学界和公众才开始关注这一主题。
人们重点关注的问题是，在癌症易感人群中，甘精胰岛素或其他胰岛素类似物是否会加快癌症的生长。会上，来自甘精胰岛素（来得时）的生产商赛诺菲-安万特公司和地特胰岛素（诺和平）的生产商诺和诺德公司的代表报告的数据显示，其相应产品与癌症之间无显著关系，不具有统计学意义。
但《糖尿病学》（Diabetologia）刊载的一项研究却得出了二甲双胍具有保护作用的证据，英国卡迪夫（威尔士）大学的Craig J. Currie博士及其助手在62,809余名糖尿病患者中开展了一项回顾性队列研究，结果发现，与接受其他糖尿病治疗的患者相比，接受二甲双胍治疗的患者罹患癌症的风险最低；并且与胰岛素单药治疗相比，二甲双胍联合胰岛素治疗可减缓癌症的进展，危险比为0.54。
《糖尿病学》（Diabetologia）的主编Edwin Gale博士评论道，目前已有多个系列的研究在探讨二甲双胍除了用于糖尿病治疗以外是否也是一种潜在的抗癌治疗。“这是当今的研究热点之一。”
除了卡迪夫大学开展的研究之外，还有研究表明，接受胰岛素或胰岛素促泌剂治疗的患者罹患实体癌的几率高于接受二甲双胍治疗的患者，与二甲双胍联用则可在很大程度上避免风险增加。二甲双胍治疗可降低出现结肠癌或胰腺癌的风险，但对罹患乳腺癌或前列腺癌的风险无影响。与使用人胰岛素相比，接受胰岛素类似物的治疗不会导致罹患癌症的风险增加（Diabetologia 2009;52:1766-77）。
同样，另一项研究也表明，使用二甲双胍可降低糖尿病患者出现胰腺癌的风险，但胰岛素或胰岛素促泌剂治疗则导致风险增加（Gastroenterology 2009;137:482-8）。
会上，Currie博士总结了英国一项观察性研究得出的最新数据。该研究以全科医疗中的患者人群为分析对象，其中31,421余名接受二甲双胍单药治疗、5,035名接受胰岛素与二甲双胍联合治疗、4,829名接受胰岛素单药治疗。经校正后发现，使用胰岛素与癌症之间存在明显的剂量-反应关系，但与二甲双胍联用可降低这一风险。
EASD主席Ulf Smith博士称，日前刚发表的两项研究进一步支持了二甲双胍可能具有抗癌保护作用的推测。其中一项研究显示，在接受二甲双胍治疗的糖尿病伴乳腺癌患者中化疗的应答率更高（J. Clin. Oncol. 2009;27:3297-302）。
另一项在线发表的研究则进一步支持了所谓“癌症干细胞”的假设，即与肿瘤中的大部分癌症细胞不同，癌症干细胞对化疗药物耐药，且能引起肿瘤中多种细胞类型再生，从而导致疾病复发。可选择性靶向作用于癌症干细胞的药物，尤其是与化疗联用，将给癌症治疗带来希望。
这项在小鼠中开展的研究表明，在4种基因类型各异的乳腺癌模型中，二甲双胍可抑制细胞转化并选择性杀死癌症干细胞，并且二甲双胍与经过严格论证的化疗药物阿霉素联合用药，可同时杀灭培养皿中的癌症干细胞和非癌症干细胞。因此，二甲双胍与化疗药物联合治疗可改善还伴有其他类型癌症的乳腺癌患者的治疗（Cancer Res. 2009 Sept. 14 [doi: 10.1158/0008-5472.CAN-09-2994]）。
瑞典Salgrenska心血管与代谢研究中心的Smith博士表示，“这些有关二甲双胍的研究结果非常令人振奋。”
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