#Metformin RCT on 41% prevention of #LongCOVID with acute #COVID19 treatment is now published in @TheLancetInfDis at: doi.org/10.1016/S1473-…
N=1126 with long term follow up (~5% lost by 9mo)
10.4% vs. 6.3% LC incidence.
Double blind RCT using identical matched placebo.
Cost $1
The distribution of symptoms reported over time was similar as others have found. The figure (a new additional from the original pre-print) displays the freq of symptoms reported over 9 months among those wih a long covid diagnosis vs. no diagnosis.
#LongCovid symptoms interfered with both the ability to work and affected leisure activities in about half of those with LC. This very, very slowly decreased over time.
As this was a 3x2 factorial randomized trial, we also looked at #ivermectin at median dose of 430 mcg/kg/d x3d and low-dose fluvoxamine.
Acute treatment of #COVID19 with either of these did not have any subsequent benefit for reducing #LongCovid
For #ivermectin, there were not any particular subgroups who appeared to benefit for preventing #LongCovid. This is very null, no effect.
Similarly, we did not observe any benefit with low dose #fluvoxamine (50mg 2x/day) for preventing #LongCovid in the Covid-Out trial.
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@TogetherTrial has completed a sensitivity analysis for its metformin outpatient #COVID19 trial
Receiving metformin was NOT an exclusion criterion for the trial. Gving 1500mg/d on top of existing metformin was not great. Odds Ratio =1.35 for ER/hospital
But Odds Ratio=0.59 if not
The overall updated results of the trial testing metformin (after some data cleaning, rerunning the results), including people taking metformin at baseline who were then randomized to receive +1500mg/d metformin XR or blinded placebo on top of all their existing meds, was:
But the more interesting sensitivity analysis of the TogetherTrial #metformin #COVID19 double-blind randomized trail is only considering those 368 particiapnts NOT already receiving metformin at baseline. #IDTwitter
37% reduction in ER visits/hospitalizations sounds similar...
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
Metformin:
Statistically significant 42% ⬇️in ER visits & #COVID19 hospitalizations
Statistically significant 58% ⬇️in 28-day hospitalization
Statistically significant 41% ⬇️in #LongCOVID
Statistically significant -0.56 log10 copies/mL mean ⬇️in viral load at Day 5 &10
@NIHCOVIDTxGuide does not recommend metformin stating that COVID-Out trial did not demonstrate a benefit of metformin in reducing the risk of hospitalization or death in patients with COVID-19.
A very declarative statement. covid19treatmentguidelines.nih.gov/therapies/misc…
Although these are all secondary endpoints of the COVID-Out trial, it is rather a stretch to be overly declarative to say that metformin did not reduce the risk of hospitalization. Guidelines panel do cite the 14-day mITT analysis, ignoring the 28-day data or ITT analysis.
As a combo blinded trial (FLV + inhaler), which one had benefit? Hard to know. In activ-6, we did not observe a benefit of inhaled fluticasone in a double blind RCT, yet UK Principle did see a benefit in open label trial with budesonide.
Importantly the #fluvoxamine dose studied here was 100mg 2x/day.
Covid-out and activ-6 both confirmed a lack of benefit of 50mg 2x/day dose.
If I gave someone 1/2 the effective dose of an HIV med & it didn't work, does that mean the med doesn't work? Or just dose was wrong?
#Paxlovid effect on reducing #COVID19 hospitalizations in vaccinated population finally revealed to the public by FDA. #IDTwitter
0.9% (3/317) paxlovid vs. 2.2% (7/314) placebo fda.gov/media/166197/d…
The relative risk reduction (RRR) of #covid19-related hospitalization was 57.5% (95%CI, -63% to 89%) with #Paxlovid in vaccinated high risk population.
Will point out that the the Hazard Ratio is also 58% for $1 of #metformin.
If one combines the EPIC-SR vaccinated + EPIC-HR seropositive groups together, then risk of #covid19 hospitalization was:
▪️ 0.5% (4/807) with #paxlovid
▪️ 1.9% (15/791) with placebo
Relative RIsk Reduction = 74% (95%CI, 22%-91%)
Number Needed to Treat = 71 (95%CI, 40-300)
Does #metformin reduce hospitalization or not? In a double-blind placebo controlled trial, 28-day data:
NIH guidelines cite the 14-day mITT data where there was not a statistical reduction.
The 14-day and 28-day ITT data also had a statistical reduction in hospitalization.
These numerical complete case data were published in NEJM.
"Through day 28, hospitalization or death occurred in 8 of 596 patients (1.3%) receiving metformin and in 19 of 601 controls (3.2%)"
(2.9% & 1.2% above are by Kaplan-Meier methodology). nejm.org/doi/full/10.10…
While the authors were not allowed to highlight these data or put a p-value in, apparently there are a lot of poeple who can't run a chi-square or fisher's exact test -- as I keep hearing that metformin didn't reduce hospitalization in the COVID-Out trial.