Metformin Reduces COVID-19 Related Deaths in Diabetic Women

Metformin reduces mortality in women infected with COVID-19 by reducing the level of inflammatory mediator called TNF-alpha. This in turn reduces the inflammatory response in the body, inflammation and subsequent cytokine storm.

According to researchers from the University of Minnesota, metformin, which is an oral anti-diabetic drug, reduces the risk of death in women infected with COVID-19. Metformin works by inhibiting the mast cell activation, that are immune system cells released during an allergic response in he body. SARS-CoV-2 infection triggers mast cells response leading to increased generation of TNF alpha, thereby causing subsequent cytokine storm, which is the main cause of fatality in COVID-19 infection.

‘Metformin in diabetic women, works by activating the AMPK pathway, that stabilizes ACE-2 receptors on cell surface and prevents them from binding with SARS-CoV-2 receptors. This reduces inflammatory response and subsequent cytokine storm, that is the main cause of death in COVID-19.’

Metformin

Metformin is antihyperglycemic drug, approved by the US Food and Drug Administration. It was originally developed to treat influenza and reducing blood sugar levels, was seen as a side-effect of the drug. It works by reducing both basal and post-prandial (after food) blood sugar levels. A previous study in Wuhan, China had stated that metformin reduces mortality in COVID-19 patients.

Metformin works by reducing the absorption of glucose from food. It also phosphorylates or adds a phosphorous group to the liver enzyme AMP-activated protein kinase, which increases use of glucose my muscles and reduces glucose production. Another benefit of metformin is that it helps over weight or obese people lose weight irrespective of their diabetic profile.

Some side effects of metformin include heartburn, diarrhoea, nausea, vomiting, bloating, gas, stomach and muscle pain. It can sometimes case a fatal condition called lactic acidosis which is the build up of lactic acid in the body causing abdominal pain, muscle pain and respiratory distress. It is contraindicated to use in people with renal impairment, who have diabetic ketoacidosis or who are allergic to the drug.

How Does Metformin Affects SARS-Cov-2?

COVID-19 mortality occurs mainly due to respiratory failure arising from acute lung injury or severe respiratory distress. These conditions cause fluid leakage in lungs. This makes breathing difficult resulting in hypoxemia or low blood oxygen levels. If enough oxygen is not circulated in the body, it leads to organ damage.

SARS-CoV-2 that causes COVID-19, penetrates into the cells by binding to the ACE-2 receptors present on their surface. When the virus enters the cell, it reduces the expression of ACE-2, increasing inflammation. Faulty ACE-2 is responsible for acute lung injury by the process called autophagy through the AMPK/mTOR pathway, where the body clears out extra or damaged cells and organelles.

Metformin activates the AMPK pathway which increases the expression of ACE-2 and makes it more stable by phosphorylating it. This phosphorylation makes ACE-2 receptors on the cell surface unable to bind with COVID-19 virus. Metformin also reduces the harmful effects of inflammation of the lungs and heart, preventing fatality.

Source: Medindia