Effects of Metformin on Clinical outcomes in Patients with Type 2 Diabetes and Covid-19

Background: The effects of metformin therapy on the prognosis of patients with coronavirus disease 2019 (COVID-19) are unclear. Objective: To review effects of metformin on clinical outcomes, particularly mortality, in patients with type 2 diabetes and COVID-19. Methods: Review of English literature by PUBMED search until April 20, 2021. Search terms included diabetes, COVID-19, metformin, Retrospective studies, meta-analyses, pertinent reviews, and consensus guidelines are reviewed. Results: All available studies in this area are retrospective. Two population-based studies did not find significant association between metformin use and susceptibility to COVID-19. Most, but not all studies, suggest that metformin use prior to hospital admission might be associated with significant decrease in mortality in patients with type 2 diabetes and COVID-19. Continuing metformin use after hospital admission did not have significant impact on COVID-19 related death but may decrease risk of acute respiratory distress syndrome (ARDS). Meanwhile, in-hospital metformin administration may be associated with approximately 4.6 times increase risk of lactic acidosis in patients with severe symptoms of COVID-19, patients taking ≥2 gm/d of metformin, and patients with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 kg/m2. Conclusions: Although most retrospective studies suggest that metformin administration may be associated with decreased risk of COVID-19 mortality, these data should be confirmed by randomized trials. In patients with type 2 diabetes and COVID-19 admitted to the hospital, metformin use should be avoided in presence of severe symptoms of COVID-19, kidney dysfunction (eGFR < 60 ml/min/1.73m2), and in daily doses of ≥ 2 gm due to increased risk of lactic acidosis.