Division of Medical Oncology Unit, EO Ospedali Galliera, Mura delle Cappuccine 14, 16128 Genoa, Italy.
Cancer Prev Res (Phila). 2010 Nov;3(11):1451-61. doi: 10.1158/1940-6207.CAPR-10-0157. Epub 2010 Oct 12.
Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched.
二甲双胍是一种降低胰岛素的药物，在糖尿病患者的流行病学研究中与降低癌症风险有关。我们进行了全面的文献检索和荟萃分析，以评估二甲双胍对糖尿病患者癌症发病率和死亡率的影响，使用 Pubmed、ISI Web of Science、Embase 和 Cochrane 图书馆，直到 2009 年 5 月，没有语言或时间限制。对有足够信息允许评估癌症风险/死亡率和不确定性度量的独立报告进行了审查，并由三位研究人员独立进行交叉核对。根据干预措施、研究人群、独立性以及癌症发病率或死亡率数据的报告，选择了 11 项相关性研究，报告了 4042 例癌症事件和 529 例癌症死亡。与使用其他抗糖尿病药物相比，服用二甲双胍的患者总体汇总相对风险降低了 31%（0.69；95%置信区间，0.61-0.79）。这种反比关系在胰腺癌和肝细胞癌中显著，而在结肠癌、乳腺癌和前列腺癌中不显著。注意到了剂量反应关系的趋势。与其他治疗方法相比，二甲双胍可降低糖尿病患者的癌症发病率风险。鉴于大多数研究的回顾性性质以及对照治疗可能增加风险，在开展大型癌症预防试验之前，需要进行 II 期临床试验。
