Metformin, an oral anti-diabetic drug, may reduce mortality in women infected by COVID-19, claims study

In research done at the University of Minnesota, a group of scientists have found that metformin, an oral anti-diabetic drug, may be helpful in reducing the risk of death by COVID-19 in women.

The findings of the study are still in the preprint phase and not yet peer-reviewed. However, as per the research, the drug reduces the levels of an inflammatory mediator called TNF-alpha, thus reducing the inflammatory response in the body. Inflammation, and the subsequent cytokine storm, is one of the proposed reasons for mortality in coronavirus patients.

Though the exact reason for the difference was not known, it was suggested that the sex hormones and certain epigenetic changes on the Y chromosome (changes in DNA that do not alter the genetic sequence but can regulate the expression of a gene) may be responsible for it. Metformin inhibits mast cell activation. Mast cells are immune system cells that are responsible for allergic reactions in the body. These cells are responsible for cytokine storms in SARS-CoV-2 infection. Studies done on rats show that mast cells are responsible for a greater increase in TNF alpha in females than males. So this may be another reason why women are benefited more from metformin.

This is not the first study that has suggested the positive effects of metformin on COVID-19 patients. Another study done earlier in Wuhan had indicated that this drug is effective in reducing mortality in coronavirus patients.

Here are four things you need to know about metformin:

What is metformin?

According to the US Food and Drug Administration, metformin is an antihyperglycemic agent that lowers both the postprandial (after meal) and basal blood glucose levels in diabetic patients.

However, not a lot of people know that metformin was not originally an antidiabetic drug. It was originally developed to treat influenza and reducing blood glucose was actually a side effect of this drug.

How does metformin work?

Metformin phosphorylates (adds a phosphorus group to) the enzyme AMPK (AMP-activated protein kinase) in liver cells. This leads to increased uptake of glucose by muscles (due to increased response to insulin) and reduced glucose production in the liver. Metformin also decreases the amount of glucose you absorb from your food.

Studies show that metformin also helps overweight and obese people lose weight regardless of whether they have diabetes or not. This probably happens by reducing the effects of insulin on body weight.

How does metformin affect SARS-CoV-2?

Acute lung injury and it’s more severe form, acute respiratory distress syndrome, are two COVID-19 complications that lead to respiratory failure and death. The conditions are characterised by fluid leakage in the lungs, making it difficult to breathe and leading to hypoxemia (low blood oxygen). If your body does not get enough oxygen, it can lead to organ damage.

It is known already that SARS-CoV-2, the causative agent of COVID-19, binds to ACE-2 receptors present on the surface of body cells to enter inside them.

Now, studies show that ACE-2 is responsible for acute lung injury in COVID-19 patients. ACE-2 brings about a process called autophagy through the AMPK/mTOR pathway. Autophagy is the process by which the human body clears out extra or damaged cells and organelles.

AMPK also increases the expression of ACE-2 and makes it more stable by phosphorylating it. This phosphorylation would make ACE-2 unable to bind to SARS-CoV-2. Since metformin activates AMPK, it may just keep the coronavirus from binding to the ACE2 receptors.

Also, it has been shown that once the virus enters inside a cell, it reduces the expression of ACE-2 receptors on the surface of those cells. This, in turn, increases inflammation. Since metformin increases the expression of ACE-2, it may also help reduce the harmful effects of inflammation on the cardiopulmonary system.

What are the side effects of metformin?

The US National Library of Medicine lists the following side effects of metformin:

• Heartburn
• Nausea
• Diarrhea
• Bloating
• Gas 
• Stomach pain
• Muscle pain

According to the FDA, metformin also carries the risk of a potentially fatal condition called lactic acidosis. Lactic acidosis is marked by lactic acid buildup in the body. When it occurs due to metformin, lactic acidosis causes symptoms like muscle pain, abdominal pain and respiratory distress.

Those who are above 65 years of age are taking certain medications, have kidney or liver conditions or consume alcohol are at increased risk of the condition.

This drug is not given to those with acute renal impairment, those who are allergic to the drug or those who have metabolic acidosis or diabetic ketoacidosis.

For more information, read our article on COVID-19 prevention tips for older people and those living with chronic illnesses.

Health articles in Firstpost are written by myUpchar.com, India’s first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health.