Thread by @boulware_dr

Metformin's benefit for #COVID19 is from an anti-viral effect.
3.6-fold greater reduction in #SARSCOV2 viral load over placebo equating to: -0.56 log10 copies/mL (95%CI, -1.05 to -0.06,p=0.027) #IDTwitter
medrxiv.org/content/10.110…

We observed no virologic effect of #ivermectin at median of 430 mcg/kg/day x3 days or of low-dose #fluvoxamine at 50mg 2x/d.
Metformin Virologic Effect was generally consistent across subgroups, larger in the unvaccinated at -0.773 log10 copies/mL (95%CI, -1.408 to -.139)

Metformin is a $1 therapy.
At Day 5 antiviral effect over placebo was 0.47 log10 copies/mL for metformin, 0.30 log10 copies/mL for molnupiravir, & 0.80 log10 copies/mL for nirmatrelvir; and at Day 10 was 0.64 log10 copies/mL for metformin and 0.35 log10 copies/mL for nirmatrelvir

That is a bit of an apples to oranges comparison as comparing nirmatelvir starting within 5 days in unvaccinated persons. No EPIC-SR data available for vaccinated pop.

0.80 log for paxlvoid unvaccinated vs 0.77 log reduction with metformin in unvaccinated is same ballpark.

The obvious question is what would happen if you combined the two meds? Nirmatelvir/ritonavir (paxlovid) + metformin or Shonigi's ensitrelvir + metformin.
(or molnupiravir+metformin... would that actually make molnupiravir more active).

If I was developing a novel antiviral for any RNA virus, I would like to see what is the added effect of adding an indirect host directed therapy such as metformin to any new virologic therapy.

Metformin summary:
⬇️ 58% reduction in COVID-related hospitalizations through 28-days
⬇️42% reductin in ER vistis/hospitalizations within 14-days
⬇️41% reduction in #LongCovid
-- No reduction in self-reported hypoxemia with inaccurate pulse oximters

https://twitter.com/boulware_dr/status/1641801211169976327

Metformin in the trial was dosed with immediate release 500mg tabs.
Day 1 : 500mg once
Day 2-5: 500mg twice daily
Day 6-14: 500mg morning, 1000mg night.

Major side effect is GI of loose stool/diarrhea with rapidly increasing the dose, hence we titrated up over several days.

Metformin is an interesting drug.
There is an extensive medical literature about metformin's effect for weight loss, which many people also need (myself included could lose 10 lbs / 5kg).
pubmed.ncbi.nlm.nih.gov/?term=metformi…

More data coming on Thursday, 6:30pm EDT.

Reduced incidence of #longcovid with acute #COVID19 treatment with metformin in a randomized clincial trial, now published.

https://twitter.com/boulware_dr/status/1666935635054034945

One difference between the antiviral effect of #paxlovid vs #metformin is that paxlovid has an effect through day 5 & then with short half-life, fades. In contrast 14 days of metformin, the antiviral effect increases over time.
At day 10, -0.64 log for MET vs. -0.35 for PAX.

This distinction on the duration of antiviral effect might be why metformin had a 41% reduction in long covid symptoms.
What would happen if people with ongoing symptoms at 14 days continued an antiviral? be it metformin or metformin + paxlovid. An interesting question???

For further basic science justification on in vitro antiviral effects of metformin, see this paper:
While in vitro lab data provide an antiviral mechanism, it is nice to see actual human data from a proper RCT to validate the in vitro lab finding.ncbi.nlm.nih.gov/pmc/articles/P…