Metformin and COVID-19: From cellular mechanisms to reduced mortality

Type 2 diabetes mellitus (T2DM) is associated with both poorer clinical outcomes during the COVID-19 pandemic and an increased risk of death in such hospitalized patients. While the role of glucose control has been emphasized to improve the prognosis, the impact of different glucose-lowering agents remains largely unknown. Metformin remains the first-line pharmacological choice for the management of hyperglycaemia in T2DM. Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with T2DM hospitalized for COVID-19. The present concise review summarizes the available data from observational retrospective studies that have shown a reduction in mortality in metformin users compared with non-users, and briefly discusses the potential underlying mechanisms that might perhaps explain this favourable impact. However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials.