@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:

#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.

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:
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…

Another confirmatory trial of beneficial effect of #fluvoxamine 100mg BID with Budesonide inhaler in a highly vaccinated population for #COVID19

Dose matters. 50mg 2x/d is not 100mg 2x/d. FLV 50mg 2x/d did not have benefit in two trials

https://twitter.com/ABsteward/status/1648074491573026817

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.

#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.

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…

Ivermectin still does not work when dosed up to 6 days at doses off 400-600 mcg/kg/day for #covid19

Read the manuscript.

We're presenting virologic data tomorrow at #CROI from Covid-OUT trial on metformin, IVM, & fluvoxamine. One is very interesting.

jamanetwork.com/journals/jama/… Editorial by the JAMA Editor in Chief which summarizes the situation.

jamanetwork.com/journals/jama/…

COVID-Out double-blind randomized trial tested #metformin, ivermectin, or fluvoxamine for outpatient #COVID19. Secondary endpoint was incidence of Long Covid (PASC).
Volunteers were followed monthly to 10 mo.
Metformin 42% reduction in Long Covid.
medrxiv.org/content/10.110… Incidence of Healthcare provider diagnosed long covid (PASC) was 42% less among those randomized to #metformin vs. matched placebo.

Hazard Ratio for Long Covid in the metformin group versus control was 0.58 (95% CI 0.38 to 0.88, P=0.009);

#Paxlovid with zero benefit in those aged <65yo with #covid19 in new @NEJM retrospective case-control study of 109,254.
Yes, a statistical benefit in >65yo (which is the headline), but no NNT mentioned. Cost might be $1/2Mil to prevent 1 hospitalization.

nejm.org/doi/full/10.10… We used to start with retrospective case-control studies and then go to RCTs. Now it seems, if $$$ then it is the reverse. #IDTwitter.