Association of Metformin with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis

Abstract Studies have demonstrated high prevalence of mortality in coronavirus disease (COVID-19) patients with type 2 diabetes mellitus; however, the effects of antidiabetic pharmacotherapy on COVID-19 complications need further exploration. The aim of the study was to explore the association of metformin use and mortality in COVID-19 patients. A literature search was conducted using the databases Medline (via PubMed) and Cochrane Central Register of Controlled Trials until February 09, 2021. Nine studies were included in the meta-analysis, including 12,684 COVID-19 patients. The meta-analysis suggested 37% lower risk of mortality in patients receiving metformin (risk ratio: 0.63; 95% confidence interval: 0.50–0.78; p  < 0.001). However, no significant difference in hospitalization days between the two groups ( p  = 0.197) was observed. The analysis revealed significantly lower risk of having obesity ( p  < 0.001), hypertension ( p  < 0.001), heart failure ( p  < 0.001), and cerebrovascular disease ( p  = 0.015) in the group receiving metformin. The analysis also demonstrated significantly lower risk of using anticoagulants ( p  = 0.015), diuretics ( p  < 0.001), and antiplatelets ( p  = 0.010) in patients receiving metformin. Our findings suggest that metformin use decreases mortality in COVID-19 patients. However, randomized studies demonstrating the consequences of metformin use are needed to understand the magnitude of the beneficial effects of metformin.