Diabetes mainstay metformin tamps down lung inflammation in COVID models

Lung X-ray
By stopping the production of an energy-storing molecule in liver cells called ATP, glucose-lowering drug metformin seems to reduce lung inflammation, a new study found. (National Institutes of Health)

The 27-year-old diabetes drug metformin has been studied for its potential use in a wide range of other disorders, including heart disease and cancer. Now researchers led by the University of California, San Diego say the diabetes mainstay might help prevent lung inflammation in patients with COVID-19.

The researchers tested metformin in a mouse model of severe lung inflammation that can result from COVID-19—a dangerous condition called acute respiratory distress syndrome (ARDS). The drug inhibited the onset of ARDS and relieved its symptoms, they reported in the journal Immunity.

The researchers discovered that metformin inhibits the activation of the “NLRP3 inflammasome,” which resides in the immune system and causes inflammatory responses. That’s because of the drug’s mechanism of action: It stops the production of an energy-storing molecule in liver cells called ATP, which helps lower glucose.

The new study’s co-author, UCSD pharmacology and pathology professor Michael Karin, Ph.D., had previously discovered a link between ATP and NLRP3 inflammasome activation. They also found that clearing damaged mitochondria—the energy centers inside cells—lowered the activity of the inflammasome and inflammation.

RELATED: The old diabetes drug metformin may find yet another role: reversing lung fibrosis

The potential utility of metformin in lung disease has been explored by other research teams. Scientists at the University of Alabama, Birmingham, for example, found that metformin reversed lung fibrosis in mice. The key, they determined, was the drug’s ability to activate AMPK, an enzyme that they believe boosts the metabolism of lung cells, allowing them to resolve fibrosis.

The UCSD researchers tied metformin’s ability to lower inflammation in ARDS to its inhibition of another enzyme, CMPK2. The effect of metformin on ARDS is “extensive,” and likely to be effective at the dose typically prescribed to diabetes patients, the authors wrote in the study.

Several observational studies have reported a link between metformin use and a reduction of mortality risk in patients with COVID-19, the UCSD team noted in the study—a phenomenon they believe their new research helps to explain, they said in a statement.