Summary: I've been taking metformin for months as protection against long COVID. I still mask everywhere, and I still take other COVID precautions, like nasal sprays, neosporin, air filters, Stoggles glasses, and getting a COVID vaccine. I am at high risk for severe COVID and long COVID, and I still plan to take paxlovid and use CPC mouthwash and nasal sprays if I get a COVID infection.

Why immediate-release metformin when paxlovid exists?

Paxlovid is harder to get outside of the US, and if you don't have health insurance or your health insurance doesn't cover it, it costs a lot.

Metformin is the second most commonly prescribed drug in the world (typically prescribed for type 2 diabetes or weight loss). So, lots of doctors prescribe it, and it is one of the least expensive medications out there.

Also, a paper published to the New England Journal of Medicine earlier this year found that Paxlovid is less effective than previously thought:

The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir–ritonavir and those who received placebo.

so using both paxlovid and immediate-release metformin at the same time might not be superfluous (and they don't interact with each other).

How effective is immediate-release metformin for COVID treatment?

There have been previous papers analyzing metformin's effectiveness for treating COVID, but the most notable study done on metformin in COVID patients (COVID-OUT) had a paper published this last May to Oxford University Press journal Clinical Infectious Diseases: Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19:

In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%.

The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo [...]. Those who received metformin were less likely to have a detectable viral load than placebo at day or day 10 [...].

Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%) [...].

Why immediate-release metformin? What about extended-release metformin?

Extended-release metformin might be ineffective for treating COVID, but we don't know for sure yet.

Conversely, an abandoned randomized trial testing extended-release metformin 1500 mg/d without a dose titration did not report improved SARS-CoV-2 viral clearance at day 7 [20].

They have a whole paragraph explaining the flaws of the failed extended-release metformin COVID study (the "Together Trial"), like randomizing people who were already taking metformin into the placebo or more metformin groups. The failed extended-release metformin/COVID study also had participants of that study start at the target dose of 1500mg/day extended-release metformin from the beginning, rather than starting at a lower dose and gradually increasing (an absolute must for metformin), which surely increased side effects.

Besides the flaws in the failed extended-release metformin/COVID study, immediate-release metformin might be more effective for your immune system:

Immediate-release metformin has higher systemic exposure than extended-release metformin, which may improve antiviral actions, but this is not known [24, 25].

So, immediate-release metformin is the thing that we know works for treating COVID, and there is no clinical evidence yet that extended-release metformin does, though that might change in the future.

There's also recent discussion in r/ZeroCovidCommunity on immediate-release metformin vs. extended-release metformin.

How to get immediate-release metformin and use it for COVID treatment?

How I did it: This last summer, I sent the immediate-release metformin/COVID paper to my endocrinologist and asked them to prescribe me metformin, and I have been taking it ever since. I take extended-release metformin because it has milder GI system effects, but if I get COVID, I will switch to immediate-release metformin for awhile.

Getting a metformin prescription might take time, so if you already have COVID, it's probably too late to consider metformin. There's lots of other reasons to take metformin, like slowing aging/living longer, lowering cancer risk, and lowering dementia and stroke risk, so in theory there's nothing wrong with taking metformin regularly without having type 2 diabetes, rather than starting once you get COVID. Speaking only for myself, I continually take extended-release metformin for its preventative effects, and I do not have type 2 diabetes.

Diabetes is one of the most common diseases for endocrinologists to treat, and metformin is the most common type 2 diabetes medication, so an endocrinologist/endocrine doctor is probably your best shot, if you already have one. Otherwise, you could ask your primary care doctor.

It goes without saying, but you don't have to mention COVID treatment as the reason to be prescribed immediate-release metformin, you could mention slowing aging, lowering cancer risk, or lowering dementia risk as a reason.

There are websites like AgelessRx that are willing to prescribe metformin for $75 to slow aging (that's the option of choice by r/ZeroCovidCommunity if you don't have a doctor who is willing to prescribe). Maybe they would be willing to prescribe immediate-release metformin too.

Starting metformin once you get a COVID infection should be effective if you start within the first week of symptom onset (that's the metric that the study used), as long you were prescribed it in advance so that it's available to you right away.

How much immediate-release metformin to take?

That's a conversation for you to have with your doctor. The important thing, though, is not to take too much metformin. I briefly made that mistake, and it made me develop a taste aversion to one of my previously-favorite foods, and temporarily reduced my appetite so that I stopped eating enough food until the dosage was lowered again. Taking too much metformin per day also shortens your lifespan instead of increasing it, so don't take too much per day.

Who should not take metformin?

Something to know about metformin is that, if you are vitamin B12-deficient or your kidneys don't work well, metformin can give you lactic acidosis.

So if you have any kidney damage or any kidney disease, taking metformin is probably a bad idea.

Avoiding B vitamin deficiency

• Metformin makes you absorb vitamin :b12: less effectively, so if you're not supplementing vitamin B12, you can get a vitamin B12 deficiency long-term.
  • If you're vitamin B12-deficient, taking metformin can cause anemia
  • If you're vitamin B12-deficient, taking metformin can cause lactic acidosis
• Metformin makes you absorb vitamin B9 (folate) less effectively, so if you're not supplementing vitamin B9, you can get a vitamin B9 deficiency long-term.
• Metformin makes you absorb vitamin B6 less effectively, so if you're not supplementing vitamin B6, you can get a vitamin B6 deficiency long-term.

In my case, I take a B complex supplement that includes B6, folate, and B12. My understanding is that if you supplement B vitamins, you don't need to worry about anemia, lactic acidosis, or other things that metformin + B vitamin deficiencies can cause unless your metformin dosage is too high.