There is growing evidence that pre-hospital use of metformin reduces mortality in patients with diabetes and sepsis; however, the effect of metformin on clinical outcomes in patients with diabetes and sepsis remains controversial. Therefore, there is a need for a systematic review and Meta-analysis of existing studies to further evaluate whether metformin can improve mortality and other clinical outcomes in patients with diabetes and sepsis.

To systematically evaluate the effects of pre-hospital metformin use on mortality, initial plasma lactate level and organ dysfunction in patients with diabetes and sepsis.

PubMed, Embase, Cochrane Library, Web of Science, Scopus, China Biomedical Literature Service System, Wanfang Data, CNKI and other databases were searched by computer for Chinese and English literature on the effects of pre-hospital metformin use on clinical outcomes in patients with sepsis and diabetes from inception to March 15, 2023. The test group (MET group) involved adult patients with diabetes and sepsis received pre-hospital metformin use, and the control group (NM group) involved adult patients with diabetes and sepsis who did not receive pre-hospital metformin use. After screening, data extraction and literature quality evaluation were conducted by two researchers, Meta-analysis was performed using RevMan 5.3 software.

A total of 12 papers were included in this study, involving 12 320 patients with diabetes and sepsis, with Newcastle-Ottawa Scale (NOS) scores of 7-8. The results of Meta-analysis showed that the mortality rate (OR=0.61, 95%CI=0.46 to 0.80, P<0.001) and the use rate of vasopressors (OR=0.83, 95%CI=0.69 to 0.98, P=0.03) in MET group were lower than those in NM group; there was no significant difference in initial plasma lactate level (MD=0.31, 95%CI=-0.12 to 0.75, P=0.16) , serum creatinine level (MD=-0.81, 95%CI=-0.48 to 0.13, P=0.25) , initial blood glucose level (MD=32.94, 95%CI=-10.12 to 76.01, P=0.13) and mechanical ventilation (OR=0.90, 95%CI=0.77 to 1.06, P=0.23) between the MET group and NM group.

The pre-hospital use of metformin can reduce the mortality of patients with diabetes and sepsis, and reduce the use rate of vasoppressors in corresponding patients, providing updated evidence that metformin can reduce the mortality of patients with diabetes and sepsis. However, whether it can reduce the sepsis severity score and reduce the maximum dose of norepinephrine in patients with diabetes and sepsis remains to be further studied.

越来越多的证据表明，入院前使用二甲双胍可降低糖尿病合并脓毒症患者的死亡率，然而，二甲双胍对糖尿病合并脓毒症患者临床结局的影响仍存在争议，因此，有必要对现有研究进行系统回顾和荟萃分析，进一步评估二甲双胍是否有利于改善糖尿病合并脓毒症患者死亡率等临床结局。

系统评价入院前使用二甲双胍对糖尿病合并脓毒症患者死亡率、初始血浆乳酸水平和器官功能障碍等的影响。

计算机检索PubMed、Embase、Cochrane Library、Web of Science、Scopus、中国生物医学文献服务系统、万方数据知识服务平台、中国知网以及其他数据库中二甲双胍对糖尿病合并脓毒症患者临床结局影响的相关中、英文文献，试验组（MET组）为入院前使用二甲双胍的糖尿病合并脓毒症的成年患者，对照组（NM组）为入院前未使用二甲双胍的糖尿病合并脓毒症的成年患者，检索时限为数据库建立至2023-03-15。由2名研究人员筛选、提取数据及评价文献质量后，采用RevMan 5.3软件进行Meta分析。

本研究共纳入12篇文献，共12 320例糖尿病合并脓毒症患者，纳入文献的纽卡斯尔-渥太华量表（NOS）评分为7~8分。Meta分析结果显示：MET组患者死亡率（OR=0.61，95%CI=0.46~0.80，P<0.001）、血管升压药的使用率（OR=0.83，95%CI=0.69~0.98，P=0.03）低于NM组；MET组与NM组患者初始血浆乳酸水平（MD=0.31，95%CI=-0.12~0.75，P=0.16）、血清肌酐水平（MD=-0.81，95%CI=-0.48~0.13，P=0.25）、初始血糖水平（MD=32.94，95%CI=-10.12~76.01，P=0.13）、机械通气（OR=0.90，95%CI=0.77~1.06，P=0.23）比较，差异无统计学意义。

入院前使用二甲双胍可以降低糖尿病合并脓毒症患者的死亡率，并可减少相应患者血管升压药的使用率，为二甲双胍可降低糖尿病合并脓毒症患者死亡率提供了全新的证据。但对于糖尿病合并脓毒症患者能否降低脓毒症严重程度评分以及减少去甲肾上腺素最大剂量仍有待进一步的研究。