Trial Report Outpatient treatment of Covid-19 and the development of Long Covid..., 2023, Bramante et al

I cant think stragight that table is unintelligible to me tbh - if the first column is for placebo - thats the only place i can see the '14%' figure?

So are they saying (or rather does the data support) that the risk of LC in the unvaccinated people within this study cohort, was double that of the vaccinated?

 

At least as far as "Has a medical provider told you that you have Long Covid?" works as being equivalent to LC. For those individuals, in this healthcare system, during this time period, based on however factors made a medical provider say so. Which it really isn't. It's frankly as far from the truth as a validated cancer screening vs. being told "I think you may have cancer" but without any validation.

 

This seems to be an interesting finding. However, I see that the subjects were overweight or obese. Metformin is used in people who are overweight with diabetes to modify sugar metabolism if I remember rightly. If it had a beneficial effect on a pre-diabetic state that made people feel generally better then that would be likely to be reflected in rates of 'LongCovid' diagnosis.

 

"Metformin is used in people who are overweight with diabetes to modify sugar metabolism if I remember rightly."
Haven't read the preprint [and only read one comment - above] but I'm guessing that it may be possible to check the relationship between sugar levels (pre-diabetic) and improvement following Metformin.

 

I take Metformin 850 mg twice a day for Poly Cystic Ovary Syndrome, & have done for about 17yrs. I am no longer overweight/obese - it had an almost miraculous effect in that respect - I lost about 3 stone over 6months without changing anything else (i already had ME for about 3yrs when i started taking it).

One wonders what the effect would be (in terms of decreasing LC risk) on people taking it all the time.

 

Now published

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

Background
Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.

Methods
We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30–85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194.

Findings
Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37–54) and median BMI was 29·8 kg/m2 (IQR 27·0–34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2–8·2) in participants who received metformin and 10·4% (7·8–12·9) in those who received identical metformin placebo (hazard ratio [HR] 0·59, 95% CI 0·39–0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15–0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59–1·64) or fluvoxamine (1·36, 0·78–2·34) compared with placebo.

Interpretation
Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.

Open access, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00299-2/fulltext

 

I guess they should’ve used an “active” placebo that also caused a similar gastro side effect as what metformin causes. Not sure how feasible that is though in practice. I’ve read trials with active placebos when a treatment has a certain smell or taste, though not wrt known side effects.

 

I'm not particularly fond of the Metformin trial for people with a normal BMI. However, if it is convincing enough for people to prove that Long-Covid isn't psychological or is the last bit of evidence they needed to reach that conclusion, as suggested in this newly published paper "The therapeutic validation of long COVID", I'm all for it:
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00355-9/fulltext

 

Would it make sense to test if Metformin could reduce the risk of ME/CFS following EBV-infection?