Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus

Coronavirus disease 2019 (COVID-19 ) is a new pandemic the entire world is facing since December of 2019. Several risk factors are identified in developing severe disease and one of which is preexisting type 2 diabetes mellitus. Metformin is known to have host-directed anti-viral and anti-inflammatory properties. However, whether these effects offer lower mortality remains unclear. In this retrospective study, we aim to address whether metformin use prior to admission decreases mortality in patients with COVID-19 and pre-existing type 2 diabetes mellitus. A total of 1356 hospitalized patients with COVID-19 and pre-existing type 2 diabetes mellitus was analyzed by multivariable regression. Covariates that potentially confound the association were further adjusted using propensity score matching or inverse probability of treatment weighting. We found that metformin therapy prior to admission in patients with COVID-19 and type 2 diabetes mellitus was significantly associated with less primary outcome events including in-hospital mortality and hospice care enrollment with an odds ratio (OR) of 0.25 (95% CI 0.06-0.74) and less in-hospital length of stay, compared to the nonmetformin group. Our results provide supporting evidence that metformin may confer increased survival in patients with COVID-19 and type 2 diabetes mellitus treated with metformin prior to hospitalization. Rapid outbreak and spread of coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leads to a global health crisis [1] [2] [3] [4] [5] . Risk factors and comorbidities linked to worse outcomes for COVID-19 patients have been identified. These include old age 5 , chronic pulmonary disease and smoking 6 , cardiovascular disease 6 , hypertension 7 , diabetes mellitus and obesity 8 . Patients with pre-existing diabetes mellitus, depending on nations and patient cohorts, have been reported to account for patients with COVID-19 from 5 to 20% in China, 17% in Lombardy in Italy to 33% in the US 1-5 . Diabetic patients hospitalized with COVID-19 are two-to three-fold more likely to be admitted into intensive care units than that of non-diabetics and the mortality rate is at least doubled 6,9-11 , suggesting urgent need for effective treatments in patients with COVID-19 and diabetes mellitus. Metformin is widely used as the first-line therapy for type 2 diabetes mellitus 12 . Metformin is effective, safe, and inexpensive and may reduce the risk for cardiovascular events and death in type 2 diabetes mellitus 13 . Historically, because of its host-directed anti-viral properties, metformin was used during the treatment of influenza outbreak 14 . Likewise, based on the pathogenesis of SARS-CoV-2, several mechanisms have been speculated about the possible beneficial effects of metformin in COVID-19 patients with pre-existing type 2 diabetes mellitus, such as anti-inflammatory effects 15 , reduction in neutrophils 16 , increasing..