Du Lili, Wang Mingli, Kang Yingying, Li Bo, Guo Min, Cheng Zhifeng, Bi Changlong
Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Oncotarget. 2017 Apr 18;8(16):26448-26459. doi: 10.18632/oncotarget.14688.
Several observational studies have shown that metformin can modify the risk and survival of colorectal cancer (CRC) in patients with diabetes mellitus, although the magnitude of this relationship has not been determined. We conducted an updated systematic review and meta-analysis to analyze the association between metformin and CRC mortality and searched relevant databases up to July 2016. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CS) and disease-free survival (DFS). Summary hazard ratios (HRs) were calculated using a random-effects model. Seventeen studies enrolling 269,417 participants were eligible for inclusion. Comparing with non-metformin users in diabetic CRC patients, the summary HRs for OS in metformin users were 0.69 (95% CI, 0.61-0.77). Subgroup analyses stratified by the study characteristics and sensitivity analysis by the trim-and-fill method (adjusted HR 0.77, 95% CI, 0.67-0.87) confirmed the robustness of the results. However, significant OS benefit was noted in patients with stage II and III disease. Five studies reported the CRC prognosis for CS and three for DFS; metformin intake was significantly associated with patient CS (HR 0.75, 95% CI, 0.59-0.94), but not DFS (HR 0.38, 95% CI, 0.13-1.17). Our findings suggest that metformin intake is associated with improved survival outcomes in terms of OS and CS in CRC patients with diabetes, particular for OS in stage II and stage III patients. Further studies should be conducted to determine CRC survival between metformin use and patient specific clinical and molecular profiles.
多项观察性研究表明，二甲双胍可改变糖尿病患者患结直肠癌（CRC）的风险及生存率，尽管这种关系的程度尚未确定。我们进行了一项更新的系统评价和荟萃分析，以分析二甲双胍与CRC死亡率之间的关联，并检索了截至2016年7月的相关数据库。主要结局为总生存期（OS）。次要结局为癌症特异性生存期（CS）和无病生存期（DFS）。采用随机效应模型计算汇总风险比（HRs）。纳入了17项研究，共269417名参与者。与糖尿病CRC患者中未使用二甲双胍的患者相比，使用二甲双胍患者的OS汇总HR为0.69（95%CI，0.61 - 0.77）。按研究特征分层的亚组分析和采用修剪填充法的敏感性分析（校正HR 0.77，95%CI，0.67 - 0.87）证实了结果的稳健性。然而，在II期和III期疾病患者中观察到显著的OS获益。五项研究报告了CS的CRC预后，三项报告了DFS的预后；二甲双胍的摄入与患者CS显著相关（HR 0.75，95%CI，0.59 - 0.94），但与DFS无关（HR 0.38，95%CI，0.13 - 1.17）。我们的研究结果表明，在糖尿病CRC患者中，二甲双胍的摄入与OS和CS方面的生存结局改善相关，特别是II期和III期患者的OS。应进一步开展研究以确定二甲双胍使用与患者特定临床和分子特征之间的CRC生存情况。
