Ivermectin failed in a high-dose trial, but metformin might help treat covid.
Metformin might lower covid hospitalization and the risk of long covid, but no one is paying attention.
Three large ivermectin trials from 2021 showed that ivermectin works poorly against covid, when given for 3 days at a dose of 400 µg/kg.
Ivermectin supporters said that these studies were designed to fail, because the drug needs to be given out for longer (at least 5 days) and at a higher dose (600 µg/kg).
A new trial came out in December, using ivermectin for 6 days at 600 µg/kg. This should be enough for anyone. It meets or exceeds the dose that ivermectin supporters at the FLCCC advise people to take.
Ivermectin still didn’t work, even at the higher dose.
600 covid patients were given ivermectin and 600 got a placebo.
34 people on ivermectin sought emergency care, compared to 36 in the control group.
4 people on ivermectin were hospitalized, compared to 2 in the control group.
1 person taking ivermectin died. No one died in the control group.
The patients recovered at the same rate as those given placeboes. Both groups recovered in an average of 11 days:
For a drug that works, you should be able to see a difference. Here’s a graph for molnupiravir and one for paxlovid:
This ivermectin study should settle the debate, but I don’t think it will.
I expect that ivermectin supporters will come up with more excuses. They’ll complain that the drug wasn’t given early enough. But 60% of the people got ivermectin within 5 days of covid symptoms, and the results are the same if you look at only those people.
So, maybe they’ll say that ivermectin only works if it’s taken with fatty food. Or they’ll just say that the trial was fraudulent.
Rather than rehash the whole ivermectin debate, I thought I’d focus on something more important. A different cheap drug does appear to treat covid.
Metformin trial results were positive
Metformin is a cheap generic drug used to treat diabetes that might also have off-label antiviral effects.
A trial called COVID-OUT tested ivermectin, fluvoxamine, and metformin against covid. The patients in the trial were all somewhat overweight (BMI > 25) but only 1.5% were diabetic.
Ivermectin failed to help any group in the trial, but metformin caused a 40% reduction in the odds someone would need medical help (like an emergency room visit or hospitalization). Breaking the results down by subgroup make it clearer that this is a real result:
The drug worked better if taken early than if taken late. It worked better for fatter patients than for skinnier ones. But it appears to have helped everyone. It helped both vaccinated and unvaccinated people. It helped young people and old people. It worked for every covid variant. Some of the subgroups are too small to get statistical significance, but the effect is likely positive for all of them.
After following the patients for 10 months, it was found that metformin also reduced the odds of long covid by 40%:
That might even be superior to Paxlovid, which reduced long covid rates by 25% in a different study.
Metformin helps prevent long covid about as well as vaccination does. The study found that vaccinated people get long covid less often:
The trial didn’t randomize who got vaccinated, so this isn’t proof. It’s possible that healthier people chose to get vaccinated and less healthy people chose not to get vaccinated. But this number is in line with various other studies, which found that vaccination reduces long covid by anywhere between 15% and 50%.
Metformin might also work with vaccination to lower long covid risk even more:
The effect was strongest for people who were not vaccinated (57% reduction in risk) but metformin still offered some benefit for vaccinated people (15% reduction).
Taking the drug earlier after getting covid again looks better than taking it later. And fatter patients get more benefits.
By contrast, ivermectin showed no effect in preventing long covid, in the COVID-OUT study:
There are still some things we don’t know.
We don’t know how metformin is helping, whether it’s an antiviral, an anti-inflammatory, or whether it’s just helping metabolic health in high-risk covid patients. There’s more research in progress.
We also don’t know if these results would replicate for all people. Everyone in the trial was somewhat overweight, with a BMI over 25. But that’s not extremely fat — for an average-height man at 5'10'’, that’s 175 pounds. For an average woman, at 5'4'’, that’s 145 pounds.
A smaller trial, done in Brazil, found no benefits for metformin. Was the difference due to weight, trial size, or some other reason?
In the best case, this drug is an antiviral that helps everyone. In the worst, it offers a significant benefit to overweight people who are at a higher risk from covid.
“Early treatment” supporters aren’t talking about metformin
Metformin might be the thing we’ve been longing for, this whole pandemic — a cheap pill that significantly reduces the risk from covid. It doesn’t need an injection, like Remdesivir or monoclonal antibodies. It doesn’t cost thousands of dollars. It has a low, known risk profile.
If we had given it out throughout the pandemic, it might have saved a few hundred thousand lives in the US, maybe millions around the world.
You’d think that the people who promoted hydroxychloroquine and ivermectin would be thrilled about this. It’s everything they hoped those two drugs would be.
The funny thing is, ivermectin supporters aren’t talking about it.
You can search Bret Weinstein’s tweets. Nothing.
Or you can search Pierre Kory’s account. Not a word.
The trial results have been public since August. Kory’s had plenty of time to tweet about it. He had enough time to tell you to not vaccinate your children for any diseases:
You can check the FLCCC’s early treatment protocol. They recommend you take ivermectin, hydroxychloroquine, and 20 other drugs and supplements to treat covid. But there’s no mention of metformin.
They still recommend you take hydroxychloroquine and ivermectin, if you get covid. They also suggest taking fluvoxamine at 25–50 mg, twice a day. The COVID-OUT trial showed that dose didn’t work. If fluvoxamine does work, it only seems to work at a higher dose — 100 mg, taken twice a day.
Steve Kirsch treated himself with 23 different drugs when he got covid. He somehow missed metformin, the one cheap drug that’s proven to work.
Metformin was in trials at the same time as ivermectin, but there was almost no attention invested in it. You could call metformin a dark horse.
In fact, the only article I ever remember reading about metformin used exactly those words. From July 31st, 2021, right in the middle of the culture wars about ivermectin, a Microbial Instincts article:
Metformin: A Pharmaceutical Dark Horse in the Face of COVID-19
An old drug with new tricks?
medium.com
In a bit of grand irony, Bret Weinstein, host of the Dark Horse podcast, missed the drug because he was too busy selling his audience on a more popular treatment.
Why aren’t “Early Treatment” supporters interested?
I’ve talked about this puzzle before. There’s a strange way in which the supporters of “early treatment for covid” don’t support any early treatments other than ivermectin and hydroxychloroquine.
Most of them are opposed to Paxlovid and Remdesivir. Steve Kirsch even recommends that you should not send anyone with covid to the hospital.
Now, there’s a cheap generic drug that might help treat covid. They could be promoting it, but they’re not.
They’re also not spending much time advocating for other drugs or supplements. The people that think that ivermectin treats covid, also think that lots of drugs and supplements treat covid. Here’s their current list, and how effective they think each one is:
Some of these may work against covid, some might not. I’m mostly suspicious of how they come up with the numbers — they think ivermectin is 60% effective when major trials find little or so effect.
The same methodology they use, to promote ivermectin, says that quercetin is just as good — they think both are about 60% effective against covid.
Quercetin is a supplement that’s sold over the counter. No one can stop you from buying it. The same is true of melatonin (they think it’s 43% effective), vitamin D (36%), zinc (28%), vitamin C (22%), and famotidine (15%).
Imagine you were really facing an international conspiracy that refused to approve ivermectin and sabotaged every large study done on the drug. Imagine that you still wanted to help people. Wouldn’t you just do a bunch of podcasts telling people to take vitamins? You could save hundreds of thousands of lives and there’s nothing the government could do to stop you.
Bret Weinstein has never tweeted about quercetin. Pierre Kory has mentioned it only once.
That’s because these people are not trying to save lives. They’re trying to sell podcasts.
It’s easy to make a conspiracy theory about some drug that the government won’t let you have. You can’t make a conspiracy theory about the government stopping you from taking quercetin or vitamins.
The government cabal isn’t going to make vitamins illegal. They couldn’t even make vitamin D illegal if they wanted to, you can get it from sunlight.
Or could they?
The FDA hasn’t been interested in metformin, either.
The National Institute of Health reviews drugs and issues guidelines for covid. They’ve reviewed the trial data and said that metformin should not be used outside of a clinical trial.
The NIH guidelines admit what was seen in the COVID-OUT trial:
There were also no benefits seen for these agents in preventing the secondary endpoints, except in the metformin arm, where the risk of the pre-specified secondary endpoint of an ED visit, hospitalization, or death was lower than in the control arm (adjusted OR 0.58; 95% CI, 0.35–0.94)
That’s right, the drug has no benefits, other than a 42% reduction in ER visits, hospitalization, or death.
The NIH pointed out that we have other drugs that work well:
Other outpatient therapies (e.g., ritonavir-boosted nirmatrelvir [Paxlovid], remdesivir, anti-SARS-CoV-2 monoclonal antibodies) have been shown to be highly effective in preventing hospitalization or death in unvaccinated patients who are at high risk of disease progression.
Monoclonal antibodies no longer work against newer strains of covid. Remdesivir works great if given early, but it’s $3,000 and needs to be injected. Paxlovid works well but it’s $700 and it interacts harmfully with many other medications so that not everyone can take it.
We don’t have enough treatments for covid, and we don’t have any cheap ones. Metformin might be able to help. It costs 4 dollars at my pharmacy.
The US government was given access to the metformin data, 6 months before the trial results were published. They sat on it and ignored it.
95% of the world’s population lives outside of the US. Most of those people have less access to covid treatments and are less able to afford expensive drugs like Paxlovid and Remdesivir. They might have wanted to know about the trial results, too.
The FDA approves drugs against covid, but there appears to be a bias — new and profitable drugs get approved easily. Repurposed generic drugs do not.
Testing for new drugs is paid for by companies. The testing pays for itself if the drugs are approved.
There’s not much money put into testing older drugs. The positive metformin study was funded by the Parsemus foundation, the Rainwater Charitable foundation, Fast Grants, and UnitedHealth Group Foundation. That’s 3 charitable non-profits and 1 health insurance company.
We’re already 3 years into the pandemic without a cheap pill approved to treat covid.
One of the metformin study’s authors, David Boulware, thinks that no one is going to pay any attention to the drug unless the trial is repeated. That could take another year. Or longer, if no one funds the trial.
In the future, we need a better way to screen cheap generic drugs against covid and other viruses. We need public funding for these trials. And we need a broader search. We needed these drugs most in 2020, and most of the research went into doing one hydroxychloroquine study after another, rather than trying other things that might work better. 400,000 patients were put in trials for hydroxychloroquine, while most other drugs were barely tested:
In the meanwhile, people on Youtube and Substack suggest alternative treatments for covid. This process is also corrupted by money. People say whatever gets the most clicks on each video or article, whether or not it’s true. So, they talk about ivermectin conspiracies. They make things up, like the false claim that ivermectin works the same way as Paxlovid.
Dr Kory is a snake oil salesman. He makes some of his money via expensive telehealth consults, charging $1,500 for a consult. A snake oil salesman doesn’t need to care what works, only what sells.
We need to improve our institutions, so the FDA can test and approve drugs faster. But relying on Youtube, Substack, and Twitter to evaluate drugs is not an alternative.
