Prognostic role of metformin intake in diabetic patients with colorectal cancer: An updated qualitative evidence of cohort studies.
Prognostic role of metformin intake in diabetic patients with colorectal cancer: An updated qualitative evidence of cohort studies.
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DOI：
10.18632/oncotarget.14688
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发表时间：
2017-04-18
期刊：
影响因子：
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通讯作者：
Bi C
中科院分区：
文献类型：
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作者：
Du L;Wang M;Kang Y;Li B;Guo M;Cheng Z;Bi C
一些观察性研究表明，二甲双胍可以改变糖尿病患者结直肠癌（CRC）的风险和生存，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综述和荟萃分析，以分析二甲双胍与CRC死亡率之间的关系，并检索了截至2016年7月的相关数据库。主要终点是总生存期（OS）。次要结局是癌症特异性生存期（CS）和无病生存期（DFS）。采用随机效应模型计算总风险比（hr）。17项研究纳入了269,417名参与者。与未使用二甲双胍的糖尿病结直肠癌患者相比，二甲双胍使用者OS的总hr为0.69 （95% CI, 0.61-0.77）。采用研究特征分层的亚组分析和采用trim- fill法进行的敏感性分析（校正HR 0.77, 95% CI, 0.67-0.87）证实了结果的稳健性。然而，II期和III期疾病患者的OS获益显著。5项研究报告了CS的CRC预后，3项报告了DFS的预后；二甲双胍摄入量与患者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，二甲双胍摄入与CRC合并糖尿病患者的OS和CS的生存结果改善有关，特别是II期和III期患者的OS。应该进行进一步的研究来确定使用二甲双胍与患者特定的临床和分子特征之间的CRC生存率。
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.