二甲双胍对糖尿病合并妇科肿瘤患者预后影响的Meta分析

Effect of metformin on the prognosis of diabetic patients combined with gynecologic cancer: A Meta-analysis

目的系统评价二甲双胍对糖尿病合并妇科肿瘤患者预后的影响。方法计算机检索Pub Med、Embase、CNKI及万方数据库于2017年3月之前发表的关于二甲双胍对糖尿病合并妇科肿瘤患者预后影响的文献资料(无语种限制),并对综述性文章的参考文献进行二次检索。由两位评价员按照纳入与排除标准独立筛选文献、提取文献特征并以Newcastle-Ottawa scale(NOS)评分法评价文献质量。主要结局指标包括总生存期(OS)和无进展生存期(PFS)。采用STATA 12.0统计软件进行Meta分析,以风险比(HR)为效应量,各效应量以95%置信区间(95%CI)表示;采用I2检验来评估异质性,采用漏斗图及Begg和Egger检验评价文章的发表偏倚情况,采用敏感性分析判定结果的稳定性。结果共纳入16篇回顾性队列研究,文献质量为6~9分。Meta分析结果显示,二甲双胍可以提高糖尿病合并妇科肿瘤患者的OS(HR=0.71,95%CI 0.59~0.85,P=0.000)。对子宫内膜癌、卵巢癌、宫颈癌3种妇科恶性肿瘤进行亚组分析,结果显示,二甲双胍能够提高糖尿病合并子宫内膜癌(HR=0.70,95%CI 0.54~0.89,P=0.004)和糖尿病合并宫颈癌(HR=0.95,95%CI 0.90~1.00,P=0.048)患者OS。经过混杂因素控制后的结果显示,二甲双胍能提高糖尿病合并卵巢癌患者的OS(HR=0.56,95%CI 0.38~0.83,P=0.004)和PFS(HR=0.45,95%CI 0.30~0.68,P=0.000)。结论二甲双胍对妇科肿瘤的预后有一定积极作用,有利于提高糖尿病合并子宫内膜癌及糖尿病合并宫颈癌患者的OS,而且能提高糖尿病合并卵巢癌患者的PFS和OS。

Objective To systematically evaluate the effect of metformin on the prognosis of diabetic patients combined with gynecologic cancer. Methods The database including PubMed, Embase, CNKI and Wangfang, were electronically searched with no language restriction from their inception to March 2017 to collect the studies about the effect ofmetformin on the prognosis of diabetic patients combined with gynecologic cancer. The references in reviews were also searched. According to the inclusion and exclusion criteria, two reviewers screened the literatures independently, extracted data and assessed methodological quality by the Newcastle-Ottawa scale. The primary end points included overall survival （OS） and progress free survival （PFS）. The outcome measures were the pooled hazard ratios （FIR） and 95% confidence intervals （95% CI）. 12 was performed in a heterogeneity assessment. Publication bias was evaluated by using Begg＇s funnel plot and Egger＇s test, and the sensitivity analysis was conducted to confirm robustness. The Meta-analysis was performed using STATA 12.0 software. Results Sixteen eligible retrospective cohort studies were included and the score of quality assessment were ranged from 6 to 9. The Meta-analysis showed that metformin could improve the OS of diabetic patients with gynecologic tumors （HR=0.71, 95%CI 0.59-0.85, P=0.000）. Subgroup analysis revealed that metformin could improve the OS of diabetic patients combined with endometrial cancer （HR=0.70, 95%CI 0.54-0.89, P=0.004） and diabetic patients combined with cervical cancer （HR=0.95, 95%CI 0.90-1.00, P=0.048）. Meanwhile metformin improved the OS （HR=0.56, 9S%CI 0.38-0.83, P=0.004） and PFS （HR=0.45, 95%CI 0.30-0.68, P=0.000） of diabetic patients with ovarian cancer after adjusting for confounders. Conclusions The use of metformin is positive for the prognosis of diabetic patients combined with gynecologic cancer. It may improve the OS of diabetic patients with endometrial cancer and diabetic patients with cervical cancer. In addition, it improves the OS and PFS of diabetic patients with ovarian cancer.