Metformin taken during acute COVID reduces risk of long COVID by 41%. ME/CFS often gets worse after COVID, so this drug may protect from such decline

[Hip]

A study found that a two week course of metformin given within 3 days of testing positive for an acute COVID infection led to 41% fewer long covid diagnoses over the following 10 months compared with people who had taken placebo.

For participants who started metformin less than 4 days after their first COVID symptoms appeared, metformin actually decreased their risk of long COVID by 63%.

The metformin dose was titrated up over the first 6 days: 500 mg on day one, 500 mg twice daily on days two to five, then 500 mg in the morning and 1000 mg in the evening from days six to fourteen.

This clinical trial also tested the efficacy of ivermectin and fluvoxamine, but found these did not prevent long COVID.

The study did not examine whether metformin might be effective against long COVID once this disease has set in, that is something that requires further research.

Article: Diabetes Drug Metformin May Reduce Long COVID Risk



Given that a PR poll found that catching COVID made about 33% of ME/CFS patients worse for at least 6 months after, in some cases greatly worse, metformin might be an interesting drug for protection against the ill effects of COVID on existing ME/CFS.

This drug could be kept in stock, and taken as a prophylactic if hit with acute COVID.

Note that a few ME/CFS patients feel absolutely ghastly even after one tablet of metformin, they react badly to this drug. So it might be worth testing a few doses of this drug before using it to protect against long COVID. I've previously taken metformin myself, and have no problems with it, but a small number of patients report feeling terrible on metformin.

 

[Hip]

Just noticed that Cort has a blog article on this: Metformin – A Long COVID, Fibromyalgia and ME/CFS Buster?

This observation by Cort raises some concerns about this study:

The first thing to notice was the high incidence of long COVID – almost 11% – in this group. The second is the lack of definition for what a diagnosis of long COVID means. It appears that the doctors decided on their own who had long COVID.

The ME/CFS form of long COVID occurs in about 1% of people who catch COVID. So if in this study 11% of people catching COVID went on to get long COVID, their definition of LC must be very broad, and would include conditions that are not the same as ME/CFS.

What we really want to know is whether metformin can help prevent people developing the ME/CFS form of long COVID.

 

[Consul]

This was in overweight and obese people.

Here is a quote from first link below.

In an email, Puntmann praised the trial organizers' use of a medication that's readily available, which she said "should be a priority of the public health research." She suggested that metformin may protect against long COVID by reducing vascular damage caused by high blood sugar levels and related immune system changes that "appear to drive the long-covid symptoms."

End quote

Apparently vascular damage can be caused by high blood sugar level through increased cAMP activity which leads to vasoconstriction as shown in link 2. There are multiple steps that are explained in the link so i keep it short here.

So there is this PDE10A finding in pwme from a uk biobank study and its unclear why it could induce mecfs. But a lower efficiency in this gene could lead to elevated cAMP as well just like the diabetes would. So this might explain the genes relevance to mecfs - it might lead to more vasoconstriction.


https://www.livescience.com/health/...by-40-in-patients-with-obesity-trial-suggests


https://www.news-medical.net/news/2...high-glucose-damages-the-vascular-system.aspx

 

[Consul]

New genetic study, could this be why metformin prevents long covid?

We also hypothesized that the genetic variants in ATP9A and INSR both contribute to dysregulated insulin signaling in subgroups of ME/CFS patients. Type 2 diabetes-related signaling pathways and insulin resistance were also a key theme within the genes associated with long COVID, and 11 of the gene targets identified in this analysis have prior associations with type 2 diabetes in the OpenTargets database (Supplementary Table 12). Metabolic dysfunction and type 2 diabetes may increase risk of developing severe acute COVID-1986 and epidemiological studies have demonstrated that there is an increased risk of developing diabetes post COVID-19 compared against controls who had not been infected with SARS-CoV-287. Furthermore, increased incidence of insulin resistance and glycemic dysregulation was observed in patients 2 months post COVID-19 and in long COVID patients31, 88.

link

 

[pattismith]

Note that a few ME/CFS patients feel absolutely ghastly even after one tablet of metformin, they react badly to this drug. So it might be worth testing a few doses of this drug before using it to protect against long COVID. I've previously taken metformin myself, and have no problems with it, but a small number of patients report feeling terrible on metformin.

people feeling bad with metformin may take low dose Methotrexate once a week, an antiinflammatory and immunomodulator drug commonly used in autoimmune diseases.

Like Metformin, methotrexate is an AMPK activator and has anti T2D effect.

Taking folinic acid 10/12 hours after the methotrexate is recommended to prevent some of the side effects.

Effect of methotrexate use on the development of type 2 diabetes in rheumatoid arthritis patients: A systematic review and meta-analysis 2020​

Results​

Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified.

Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43).

Conclusion​

Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate.

This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337336/

 

[pattismith]

Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of “Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate”​

however I can't find any study about the impact of Methotrexate on long covid.
I guess a low dose may be better with less induced immunodeficiency...

 

[SWAlexander]

I guess a low dose may be better

Yes, it is. Methotrexate is a double-edged sword. I was on MTX (2022) for one month but had to stop because of bleeding and excessive hair loss. On the other side symptoms of inflammation (ANA) Lupus were way down.
Keep in mind, that the liver is not tolerating MTX very well and must be monitored every 14 days.

Prof. Tate NZ wrote back to me: "Methotrexate has a relatively good drug profile and regarded as relatively safe if used for a short time..."

Immunosuppressant Drugs for Lupus​

https://www.webmd.com/lupus/immunosuppressant-drugs-lupus​

 

[godlovesatrier]

Anyone tried metformin again since this was posted?

 

[pattismith]

Yes, it is. Methotrexate is a double-edged sword. I was on MTX (2022) for one month but had to stop because of bleeding and excessive hair loss. On the other side symptoms of inflammation (ANA) Lupus were way down.
Keep in mind, that the liver is not tolerating MTX very well and must be monitored every 14 days.

Prof. Tate NZ wrote back to me: "Methotrexate has a relatively good drug profile and regarded as relatively safe if used for a short time..."

Immunosuppressant Drugs for Lupus​

https://www.webmd.com/lupus/immunosuppressant-drugs-lupus​

what was your regimen with MTX?

Anyone tried metformin again since this was posted?

Metformin makes my lactates to raise and I couldn't tolerate it

 

[SWAlexander]

what was your regimen with MTX?

once a week.
Folic acid exactly 24 hours later.

 

[pattismith]

once a week.
Folic acid exactly 24 hours later.

17.5 mg MTX injection is a rather high dose.

The lowest dose is 2.5 mg per os, I guess hepatic and hematologic side effects are very rare with this lowest dose. However mental side effects are not rare even with low dose, and especially in people like us who have some special sensitivity. I will explain why MTX is a challenge for most of us, but not in this thread where I am of topic...

 

[SWAlexander]

17.5 mg MTX injection is a rather high dose.

Yes, I was in a very bad condition. I barely could walk or hold a cup of coffee, my brain was on fire and my whole body looked like this:

 

[SWAlexander]

Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial​

Interpretation​

Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype.
https://www.thelancet.com/journals/...23)01572-6/fulltext?dgcid=raven_jbs_aip_email