Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro (CH), Chieti, Italy.
PLoS One. 2013 Aug 2;8(8):e71583. doi: 10.1371/journal.pone.0071583. Print 2013.
AIMS/HYPOTHESIS: Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.
MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.
Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.
CONCLUSIONS/INTERPRETATION: Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
目的/假设：糖尿病的治疗方法与癌症风险的增加或降低有关。目前正在就二甲双胍的潜在保护作用进行争论。本文旨在总结关于二甲双胍与糖尿病患者癌症风险和癌症死亡率之间关联的证据。
MEDLINE 和 EMBASE（1966 年 1 月至 2012 年 4 月）。我们选择了比较二甲双胍和其他降血糖药物的随机研究和探索二甲双胍暴露与癌症之间关联的观察性研究。结果是癌症死亡率、所有恶性肿瘤和特定部位的癌症。
在 25307 条引用文献中，有 12 项随机对照试验（21595 名患者）和 41 项观察性研究（1029389 名患者）符合纳入标准。在观察性研究中，暴露于二甲双胍与癌症死亡风险显著相关[6 项研究，24410 名患者，OR：0.65，95%CI：0.53-0.80]，所有恶性肿瘤[18 项研究，561836 名患者，OR：0.73，95%CI：0.61-0.88]，肝脏[8 项研究，312742 名患者，OR：0.34；95%CI：0.19-0.60]，结直肠癌[12 项研究，871365 名患者，OR：0.83，95%CI：0.74-0.92]，胰腺[9 项研究，847248 名患者，OR：0.56，95%CI：0.36-0.86]，胃癌[2 项研究，100701 名患者，OR：0.83，95%CI：0.76-0.91]和食管癌[2 项研究，100694 名患者，OR：0.90，95%CI：0.83-0.98]。在随机试验中未观察到风险的显著差异。二甲双胍与乳腺癌、肺癌、卵巢癌、子宫癌、前列腺癌、膀胱癌、肾癌和黑色素瘤的风险无关。
结论/解释：结果表明，二甲双胍可能与癌症风险和癌症相关死亡率的显著降低有关。需要专门设计的随机试验来评估二甲双胍作为抗癌药物的疗效。
