Therapeutic Potential of Metformin in COVID-19: Reasoning for its Protective Role

Samuel, Samson Mathews; Varghese, Elizabeth; Büsselberg, Dietrich

SARS-CoV-2 infections present with increased disease severity and poor clinical outcomes in diabetic patients compared with their non-diabetic counterparts. Diabetes/hyperglycemia-triggered endothelial dysfunction and hyperactive inflammatory and immune responses are correlated to two- to three-fold higher intensive care hospitalizations and more than twice the mortality among diabetic COVID-19 patients. While comorbidities such as obesity, cardiovascular disease, and hypertension worsen the prognosis of diabetic COVID-19 patients, COVID-19 infections are also associated with new-onset diabetes, severe metabolic complications, and increased thrombotic events in the backdrop of aberrant endothelial function. While several antidiabetic medications are used to manage blood glucose levels, we discuss the multi-faceted ability of metformin to control blood glucose levels, attenuate endothelial dysfunction, inhibit viral entry, and infection and modify inflammatory and immune responses during SARS-CoV-2 infections. These actions make it a viable candidate for drug repurposing and the higher ground against the SARS-CoV-2 induced tsunami in diabetic COVID-19 patients.