Did you know that metformin was initially intended to be used as an influenza drug, with glucose reduction being one of its side effects? It is referred to as the ‘aspirin of the 21st century’ owing to its many pleiotropic effects.

Metformin acts by activating AMP-activated protein kinase (AMPK) in hepatocytes by causing its phosphorylation. Metformin activates AMPK via liver kinase B1 (LKB1), inhibiting the mammalian target of rapamycin (mTOR) pathway. It has been reported that the P13/AKT/mTOR pathways play a crucial role in MERS-CoV infection. Considering that metformin inhibits the same pathway, it gives an exciting lead in evaluating its role against SARS-CoV-2. Based on its inhibition of mTOR signalling, metformin might be used as an indirect modulator of the protein-protein complex, thereby preventing viral replication and pathogenesis.

The first study of COVID-19, CORONADO study intended to analyze the effect of disease in the hospitalized patients with diabetes suggested that one in ten patients dies within seven days of hospital admission, and one in five is intubated and placed on mechanical ventilation. The study was published in the journal Diabetologia.

The study reported that metformin use was linked with a reduced risk of early death, which may be reflective of a less advanced stage of diabetes with lesser comorbid conditions such as severe chronic kidney disease. Amongst the patients included in the study, 56.6% of the patients were on metformin therapy, and it was seen that number of deaths were lower in those who were on prior metformin use. However, patients on insulin therapy, RAAS blockers, β-blockers, loop diuretics and MRAs were found to be associated with death on day 7.

It is established that type 2 diabetes and COVID-19 share a bidirectional relationship. Given its pleiotropic effects and a possible role in fighting against hepatitis C virus, hepatitis B virus and human immunodeficiency virus through increasing insulin sensitivity, metformin can be a big bet in the treatment of COVID-19.

Reference

1. Sharma S, Ray A, Sadasivam B. Metformin in COVID_19: A possible role beyond diabetes. Diabetes Res ClinPract. 2020; 164: 108183.
2. Cariou B, et al. Phenotypic characteristics, and prognosis of inpatients with COVID 19 and diabetes: the CORONADO study. Diabetologia. 2020; 63:1500-1515.