How Metformin Reduces Long COVID Risk By 63%

Like GLP-1 receptor agonists, metformin was first developed for type 2 diabetes management, before enjoying wider-scale use as a weight loss drug with some other fringe benefits.

Metformin works in 3 main ways:

• it decreases glucose absorption from the gut
• it decreases glucose production in the liver
• it increases insulin sensitivity (for why this matters, see: Improve Your Insulin Sensitivity!)

It doesn’t change how much insulin is secreted, and is unlikely to cause hypoglycemia, making it relatively safe as diabetes drugs go.

You can read more about these aspects of it, here: Metformin For Weight-Loss & More

Its benefits don’t stop there, though! See also: How Metformin Slows Aging

And there’s more…

Metformin vs long COVID

Researchers (Dr. Carolyn Bramante et al.) have put together a lot of recent research, including randomized trials and epidemiological data, showing that starting metformin even during acute COVID infection (i.e. it doesn’t have to be taken prophylactically beforehand) still consistently reduces long COVID risk.

You might be wondering: why would a diabetes drug help after a viral infection? Metformin exerts these effects by means of modulating inflammation and cellular metabolism, rather than attacking a virus directly:

❝In 2020, observational, in silico computer modeling and in vitro studies of SARS-CoV-2 added to the rationale for studying metformin as acute SARS-CoV-2 treatment. Given these multiple streams of evidence, metformin’s low cost, wide availability, tolerability, and safety with no need for monitoring during short-term use, it was important to test metformin versus placebo for outpatient treatment of SARS-CoV-2.❞

~ Dr. Carolyn Bramante

The strongest evidence (albeit for the weakest claims) came from the COVID-OUT randomized trial, where people who took metformin during acute infection had a 41% lower risk of being diagnosed with long COVID over 10 months compared with placebo.

You can read that one here: Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial

So, Dr. Bramante and her team did a second major randomized trial, ACTIV-6, which confirmed similarly, finding a 50% reduction in long COVID risk, including among people with normal body weight, prior infections, vaccination, and Omicron-era infections (i.e., those who often benefit the least from novel interventions).

You can find that paper here: Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial

However! The effect was much more striking when treatment began within 3 days of symptom onset, cutting risk by 63%.

You can read about that, here: Preventing Long COVID With Metformin

It gets better; a small mechanistic randomized trial testing metformin versus placebo on viral load found metformin reduced the viral load by 93.2%

That’s the viral load, not long COVID risk, but still, it’s worth mentioning since long COVID risk is of course in large part mediated by viral load (can’t have a persistent infection if the viral load is “two” or something).

You can read that paper, here: Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial

Dr, Bramante and her team argue that adding metformin to treatment guidelines for non-hospitalized adults* could help translate this evidence into real-world prevention.

^{*Like you, dear reader, unless you are reading this from hospital, in which case, our condolences, and we hope things get better for you soon!}

Want to learn more?

Check out:

What Can Be Done About Long COVID? ← scientists have found a possible cure, a procedure known as epipharyngeal abrasive therapy, which as enjoyable as it sounds, and is not yet proven to cure it completely (although to give it its due, the science so far really is promising)

Take care!