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Background 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. Objective 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. Methods 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. Results 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