8 ms·

TLDR: > By day 300 of follow-up, 93 (8.3%) of 1,126 participants said they had received a diagnosis of long COVID by a provider. The cumulative incidence of lo

TLDR: > By day 300 of follow-up, 93 (8.3%) of 1,126 participants said they had received a diagnosis of long COVID by a provider. The cumulative incidence of long COVID by day 300 in those who took a 14-day course of metformin was 6.3% (95% confidence interval [CI], 4.2 to 8.2) compared to 10.4% (7.8 to 12.9) in the placebo group, or 39.4% lower. Interestingly, half of the participants in the study (which took place starting in December of 2020) were unvaccinated. The researchers noted that metformin appears to have reduced the viral load greatly. I wonder if that is equally true for vaccinated and unvaccinated patients. It would seem plausible (not a doctor) that the reduction in viral load is related to the lower incidence of long COVID. Now that we're in 2023, and pretty much everyone is either multiply-vaccinated or has had COVID, the study might turn out differently. If anyone has looked into the paper/data, I'd be interested to know whether the benefit is equal among vaccinated/non-vaccinated.

carlmr 3y ago
>Now that we're in 2023, and pretty much everyone is either multiply-vaccinated ~or~ and has had COVID multiple times Isn't this the most common demographic?
- kramerger 3y ago
  Not in places were vaccine rollout was quick and frictionless with good coverage, thus reducing probability of transmission of the main strain and early mutations. I think a lot of people in Northern Europe have either never had covid or had a mild possibly unnoticeable infection
  - mensetmanusman 3y ago
    No, the r0 is too high. Essentially everyone eventually gets Covid, vaccination or not, it's just that it's not worth testing continuously to see if your zero-symptom-life is currently infected.
    - Izkata 3y ago
      > to see if your zero-symptom-life is currently infected No symptoms = not having COVID-19, GP was using the term correctly. Conflating SARS-CoV-2 with COVID-19 is a big annoyance I have with the general usage of "covid".
      - taeric 3y ago
        What? Googling "asymptomatic covid" seems to disagree with this assertion? Even the wikipedia page for it claims: "At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time." Has terminology moved on?
        sudosysgen 3y ago
        The disease and the virus are two different things in standard medical parlance.
        taeric 3y ago
        I'm not sure I follow, honestly. If you are trying to hold colloquial use to a technical measure, good luck. Even https://en.wikipedia.org/wiki/COVID-19_naming https://en.wikipedia.org/wiki/COVID-19_naming has "While COVID-19 refers to the disease and SARS-CoV-2 refers to the virus which causes it, referring to the "COVID-19 virus" has been accepted." Meaning, that ship sailed. More, https://en.wikipedia.org/wiki/COVID-19 https://en.wikipedia.org/wiki/COVID-19, clearly talks about people having the disease but not being symptomatic. Such that you may be building a false divide? Yes, the virus is different from the disease. That does not imply that you only have the disease if you have symptoms.
        prottog 3y ago
        > That does not imply that you only have the disease if you have symptoms. Not the GP, but I've heard their perspective before from others, i.e. in medicine the symptom is the disease (or that the disease is defined by the symptom). If you have some virus in you that never does anything, you don't have a disease.
  - Slava_Propanei 3y ago
    [dead]
bsder 3y ago
Derek Lowe has a good discussion as well: https://www.science.org/content/blog-post/long-covid-shows-card https://www.science.org/content/blog-post/long-covid-shows-c... One thing to point out--this study provides the first really solid evidence that Long Covid actually exists. From Derek Lowe: "An overarching point, though, is made in a valuable commentary in the same issue of the Lancet by Jeremy Samuel Faust: this effect against a placebo control really shows us that there is something there. Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have"
- Llamamoe 3y ago
  There are literally thousands of studies about long COVID- unless you believe they were all hallucinations by people who shouldn't be in academia, this is very much so not the "first" really solid evidence. I've seen evidence of increased all-cause mortality, arterial stiffness, reduced physical fitness, and much, much more. All of which is in the first place only necessary because a core pillar of healthcare is the neglect and misattribution of mind-affecting disorders as psychosomatic. I know people after brain injury now being treated for "depression" instead of pituitary dysfunction that occurs in ~80% of cases.
  - Sakos 3y ago
    I think you're misinterpreting it. The full quote: > Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have: > When a disease is too poorly defined, it follows that it is almost impossible to modify either the incidence of that disease or the distribution of its outcomes—that is, unless the treatment effect is so great, and the true target population so common in the assembled denominator, that any corresponding signal dilutions are offset. The present study suggests that, even with definitions as amorphous and heterogenous as those currently in use for diagnosing long COVID, there was to be found within this study population an ample cohort of individuals with syndromes similar enough that disease incidence could be modified, and metformin appeared to achieve that. Furthermore, the finding that long COVID is modifiable, although here showing prevention, offers hope. . . This is definitely the first time I've seen anything showing a reliable effect on long Covid. Pretty much everything else I've seen has been a collective shoulder shrug of "well, we saw this, and it's maybe something about Covid, but we really don't know, and we have no idea how to treat this" and a bunch of people saying "it's just a possible side effect of an infection, we've been seeing this for decades". I have no idea how you can dismiss this as something we already know and that this isn't a positive and meaningful step forward.
snemvalts 3y ago
It was also tested only in overweight and obese patients. Pretty much most people are overweight and obese in the US as well, I wouldn't draw any results from this study for people at normal weight.
- stuff4ben 3y ago
  That is a terrible conclusion to draw. BMI is a horrible indicator of health and to say that this study has no merit to "normal" people is idiotic. Also the jab against people in the US doesn't have any place in a scientific discussion of this study. Keep your prejudices to yourself next time.
  - stjohnswarts 3y ago
    BMI is fine as an indicator of "are you fat or not", UNLESS you are a very fit athlete. However being fat and being unhealthy aren't 1 to 1, contrary to popular bias and stereotypes. I've known plenty chubby and healthy people. They might not run marathons but get on with their lives just fine. Certainly it can raise your chances of being unhealthy but it's certainly not 1:1 as many online "experts" seem to claim.
- Spooky23 3y ago
  Metformin is prescribed mostly as a first line type 2 diabetes drug. It’s also used off label for things like PCOS. So it would make sense that the folks whom benefited tended to be overweight.
r0l1 3y ago
Multiple-vaccinated or has had Covid? Why only those two options? I and a big portion of my circle is unvaccinated, healthy and didn't have Covid.
- azangru 3y ago
  A big portion? Wow. I thought no-one escaped omicron BA.2
  - r0l1 3y ago
    Can't say too much about it. Didn't really follow the whole Covid discussion and just continued my lifestyle. Eating healthy (fresh self-made food), doing sports and looking after a good mental state. Family and my circle did the same. Friends who have been vaccinated got Covid several times. But are also good now... My grandmom (89 years), also unvaccinated, didn't get Covid. Her sister got it (vaccinated). Both healthy now... Just let everybody do their own thing... The whole hate in the communities was unnecessary.
    - op00to 3y ago
      Did you get a test to see if you actually avoided Covid?
      - r0l1 3y ago
        We did normal Covid tests for work. Maybe I should do an antibody test. Would be interesting...
        mistrial9 3y ago
        antibodies are only measurable for a short time; long-term ability to defend is "learned" by the immune system but not measurable in any ordinary way; here in California coastal area there is a lot of social pressure about vaccination. Random people still insist that vaccination is important for healthy adults and sometimes under-18.
xattt 3y ago
If the inconvenience of having a vaccine are a turn-off for this demographic, I can’t imagine that GI distress (i.e. urgency) associated with metformin would be tolerable either.
- Slava_Propanei 3y ago
  [dead]
contravariant 3y ago
Hmm, going by those confidence intervals this doesn't look significant, or is that just me?
- SEMW 3y ago
  The fact that the 95% confidence intervals of two variables have some overlap doesn't mean there's a >5% chance that the expected values of the two variables are the same. Consider two independent random variables X and Y; the chance that (a sample from X is above the 90th percentile of the true distribution of X) is 10%, but the chance that (a sample of X is above the 90th percentile of the true distribution of X AND a sample of Y is below the 10th percentile of the true distribution of Y) is 1%. (disclaimer: with actual science the stats are a lot more complicated and you can't just assume they're independent and multiply the two, it's just a simplified example to give intuition about why overlapping confidence intervals don't imply what the parent thought, IANAstatistician)
  - spywaregorilla 3y ago
    Mostly false. Overlapping confidence intervals does not mean > x% chance that the two variables' expected values are the same. If the intervals overlap, the difference is not statistically significant. Your example about random variables is largely misinformed. You're talking about things as if they are individual values. But we're talking about sample means. The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n. The joint probability of getting two sample means above X threshold is irrelevant. Confidence intervals don't tell you what the probability of the true mean being above X is. They tell you, bluntly, the range of values where the true mean could be, with 95% confidence ("If i were to do this experiment 100 times, based on the results I got, I would expect the true mean to be within this range") You can play with some numbers and methods but you can rest pretty sure that a material effect size is probably not rigorously evidenced if the intervals overlap
    - SEMW 3y ago
      > If the intervals overlap, the difference is not statistically significant. Demonstrably false. Obvious counterexample: the study in the OP, which has overlapping confidence intervals and a statistically significant difference. Proof: just calculate the 95% confidence interval for the difference between the two means. You can figure out what the stddev was from half the confidence interval divided by the z-score for a 95% confidence interval, 1.96, and you get 1.02 and 1.30 for the two groups. Then the confidence interval is: (10.4 - 6.3) +/- 1.96*sqrt(1.02^2 + 1.30^2) gives [0.86, 7.34]. This does not include 0, therefore the difference is significant. > The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n. I was trying to give a basic intuition about normal distributions with a simple example, the distribution of one sample is a simpler example of a different normal distribution. Yes obviously the distribution of an estimate of X given lots of samples is not the same as the distribution of a single sample, I never claimed it was.
superkuh 3y ago
If Metformin reduces the viral load, it probably does so throughout the entire body. Whereas intramuscular vacccination leads to good protection against serious disease through humoral (body serum) immunity, it does not, unfortunately, provide significant protection to the other immune compartments like the upper respiratory mucosal layer (served by a different set of antibodies than the humoral). So this is good. This (and paxlovid) can help protect those remaining unprotected tissues of the upper respiratory that tend to be the first infected. It should be a good temporary mitigation until the USA and other countries approve of good intranasal sars-cov-2 vaccine boosters like India has (Innovac).
- thatguy0900 3y ago
  I honestly can't imagine taking more covid vaccines. I haven't even thought about covid for a year now.
  - unsupp0rted 3y ago
    People with long covid have thought about it a lot during the last year
  - QuantumGood 3y ago
    Some of us think 7 million dead is a lot, and find it harder to ignore than you do.
    - PraetorianGourd 3y ago
      3.4 million people die every year in the US. What makes these deaths acceptable but COVID a tragedy? And yes, many of those 3.4 million are preventable.
      - QuantumGood 3y ago
        It's fine if you want to make a point about COVID deaths—go ahead and say what you mean to say. I get there are many things to be said. But it's unclear why you're involving my comment with your soapbox. The parent comment to mine was about "not thinking about COVID". Why not just say what you mean to say in full? There is no need to try to put words into someone else's mouth to speak up for what you believe. You seem to simply be re-framing my comment in order to make yours. One way to start is along the lines of "This makes me think of an aspect of [the topic] which is [...] and what I think about that is [...]". (No one brought up or said any of those other deaths were acceptable. Nor did I say that COVID deaths were unacceptable or "tragic".)

carlmr 3y ago

>Now that we're in 2023, and pretty much everyone is either multiply-vaccinated ~or~ and has had COVID multiple times Isn't this the most common demographic?

kramerger 3y ago
Not in places were vaccine rollout was quick and frictionless with good coverage, thus reducing probability of transmission of the main strain and early mutations. I think a lot of people in Northern Europe have either never had covid or had a mild possibly unnoticeable infection
- mensetmanusman 3y ago
  No, the r0 is too high. Essentially everyone eventually gets Covid, vaccination or not, it's just that it's not worth testing continuously to see if your zero-symptom-life is currently infected.
  - Izkata 3y ago
    > to see if your zero-symptom-life is currently infected No symptoms = not having COVID-19, GP was using the term correctly. Conflating SARS-CoV-2 with COVID-19 is a big annoyance I have with the general usage of "covid".
    - taeric 3y ago
      What? Googling "asymptomatic covid" seems to disagree with this assertion? Even the wikipedia page for it claims: "At least a third of the people who are infected with the virus do not develop noticeable symptoms at any point in time." Has terminology moved on?
      - sudosysgen 3y ago
        The disease and the virus are two different things in standard medical parlance.
        taeric 3y ago
        I'm not sure I follow, honestly. If you are trying to hold colloquial use to a technical measure, good luck. Even https://en.wikipedia.org/wiki/COVID-19_naming https://en.wikipedia.org/wiki/COVID-19_naming has "While COVID-19 refers to the disease and SARS-CoV-2 refers to the virus which causes it, referring to the "COVID-19 virus" has been accepted." Meaning, that ship sailed. More, https://en.wikipedia.org/wiki/COVID-19 https://en.wikipedia.org/wiki/COVID-19, clearly talks about people having the disease but not being symptomatic. Such that you may be building a false divide? Yes, the virus is different from the disease. That does not imply that you only have the disease if you have symptoms.
        prottog 3y ago
        > That does not imply that you only have the disease if you have symptoms. Not the GP, but I've heard their perspective before from others, i.e. in medicine the symptom is the disease (or that the disease is defined by the symptom). If you have some virus in you that never does anything, you don't have a disease.
- Slava_Propanei 3y ago
  [dead]

bsder 3y ago

Derek Lowe has a good discussion as well: https://www.science.org/content/blog-post/long-covid-shows-card https://www.science.org/content/blog-post/long-covid-shows-c... One thing to point out--this study provides the first really solid evidence that Long Covid actually exists. From Derek Lowe: "An overarching point, though, is made in a valuable commentary in the same issue of the Lancet by Jeremy Samuel Faust: this effect against a placebo control really shows us that there is something there. Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have"

Llamamoe 3y ago
There are literally thousands of studies about long COVID- unless you believe they were all hallucinations by people who shouldn't be in academia, this is very much so not the "first" really solid evidence. I've seen evidence of increased all-cause mortality, arterial stiffness, reduced physical fitness, and much, much more. All of which is in the first place only necessary because a core pillar of healthcare is the neglect and misattribution of mind-affecting disorders as psychosomatic. I know people after brain injury now being treated for "depression" instead of pituitary dysfunction that occurs in ~80% of cases.
- Sakos 3y ago
  I think you're misinterpreting it. The full quote: > Long Covid is looking less like a cloudy mass of speculation and shoulder-shrugging, and more like a problem that medical science can start to unravel, using the tools we already have: > When a disease is too poorly defined, it follows that it is almost impossible to modify either the incidence of that disease or the distribution of its outcomes—that is, unless the treatment effect is so great, and the true target population so common in the assembled denominator, that any corresponding signal dilutions are offset. The present study suggests that, even with definitions as amorphous and heterogenous as those currently in use for diagnosing long COVID, there was to be found within this study population an ample cohort of individuals with syndromes similar enough that disease incidence could be modified, and metformin appeared to achieve that. Furthermore, the finding that long COVID is modifiable, although here showing prevention, offers hope. . . This is definitely the first time I've seen anything showing a reliable effect on long Covid. Pretty much everything else I've seen has been a collective shoulder shrug of "well, we saw this, and it's maybe something about Covid, but we really don't know, and we have no idea how to treat this" and a bunch of people saying "it's just a possible side effect of an infection, we've been seeing this for decades". I have no idea how you can dismiss this as something we already know and that this isn't a positive and meaningful step forward.

snemvalts 3y ago

It was also tested only in overweight and obese patients. Pretty much most people are overweight and obese in the US as well, I wouldn't draw any results from this study for people at normal weight.

stuff4ben 3y ago
That is a terrible conclusion to draw. BMI is a horrible indicator of health and to say that this study has no merit to "normal" people is idiotic. Also the jab against people in the US doesn't have any place in a scientific discussion of this study. Keep your prejudices to yourself next time.
- stjohnswarts 3y ago
  BMI is fine as an indicator of "are you fat or not", UNLESS you are a very fit athlete. However being fat and being unhealthy aren't 1 to 1, contrary to popular bias and stereotypes. I've known plenty chubby and healthy people. They might not run marathons but get on with their lives just fine. Certainly it can raise your chances of being unhealthy but it's certainly not 1:1 as many online "experts" seem to claim.
Spooky23 3y ago
Metformin is prescribed mostly as a first line type 2 diabetes drug. It’s also used off label for things like PCOS. So it would make sense that the folks whom benefited tended to be overweight.

r0l1 3y ago

Multiple-vaccinated or has had Covid? Why only those two options? I and a big portion of my circle is unvaccinated, healthy and didn't have Covid.

azangru 3y ago
A big portion? Wow. I thought no-one escaped omicron BA.2
- r0l1 3y ago
  Can't say too much about it. Didn't really follow the whole Covid discussion and just continued my lifestyle. Eating healthy (fresh self-made food), doing sports and looking after a good mental state. Family and my circle did the same. Friends who have been vaccinated got Covid several times. But are also good now... My grandmom (89 years), also unvaccinated, didn't get Covid. Her sister got it (vaccinated). Both healthy now... Just let everybody do their own thing... The whole hate in the communities was unnecessary.
  - op00to 3y ago
    Did you get a test to see if you actually avoided Covid?
    - r0l1 3y ago
      We did normal Covid tests for work. Maybe I should do an antibody test. Would be interesting...
      - mistrial9 3y ago
        antibodies are only measurable for a short time; long-term ability to defend is "learned" by the immune system but not measurable in any ordinary way; here in California coastal area there is a lot of social pressure about vaccination. Random people still insist that vaccination is important for healthy adults and sometimes under-18.

xattt 3y ago

If the inconvenience of having a vaccine are a turn-off for this demographic, I can’t imagine that GI distress (i.e. urgency) associated with metformin would be tolerable either.

Slava_Propanei 3y ago
[dead]

contravariant 3y ago

Hmm, going by those confidence intervals this doesn't look significant, or is that just me?

SEMW 3y ago
The fact that the 95% confidence intervals of two variables have some overlap doesn't mean there's a >5% chance that the expected values of the two variables are the same. Consider two independent random variables X and Y; the chance that (a sample from X is above the 90th percentile of the true distribution of X) is 10%, but the chance that (a sample of X is above the 90th percentile of the true distribution of X AND a sample of Y is below the 10th percentile of the true distribution of Y) is 1%. (disclaimer: with actual science the stats are a lot more complicated and you can't just assume they're independent and multiply the two, it's just a simplified example to give intuition about why overlapping confidence intervals don't imply what the parent thought, IANAstatistician)
- spywaregorilla 3y ago
  Mostly false. Overlapping confidence intervals does not mean > x% chance that the two variables' expected values are the same. If the intervals overlap, the difference is not statistically significant. Your example about random variables is largely misinformed. You're talking about things as if they are individual values. But we're talking about sample means. The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n. The joint probability of getting two sample means above X threshold is irrelevant. Confidence intervals don't tell you what the probability of the true mean being above X is. They tell you, bluntly, the range of values where the true mean could be, with 95% confidence ("If i were to do this experiment 100 times, based on the results I got, I would expect the true mean to be within this range") You can play with some numbers and methods but you can rest pretty sure that a material effect size is probably not rigorously evidenced if the intervals overlap
  - SEMW 3y ago
    > If the intervals overlap, the difference is not statistically significant. Demonstrably false. Obvious counterexample: the study in the OP, which has overlapping confidence intervals and a statistically significant difference. Proof: just calculate the 95% confidence interval for the difference between the two means. You can figure out what the stddev was from half the confidence interval divided by the z-score for a 95% confidence interval, 1.96, and you get 1.02 and 1.30 for the two groups. Then the confidence interval is: (10.4 - 6.3) +/- 1.96*sqrt(1.02^2 + 1.30^2) gives [0.86, 7.34]. This does not include 0, therefore the difference is significant. > The probability that a sample mean for a large sample is above the 90th percentile is massively lower than 10%, and depends on n. I was trying to give a basic intuition about normal distributions with a simple example, the distribution of one sample is a simpler example of a different normal distribution. Yes obviously the distribution of an estimate of X given lots of samples is not the same as the distribution of a single sample, I never claimed it was.

superkuh 3y ago

If Metformin reduces the viral load, it probably does so throughout the entire body. Whereas intramuscular vacccination leads to good protection against serious disease through humoral (body serum) immunity, it does not, unfortunately, provide significant protection to the other immune compartments like the upper respiratory mucosal layer (served by a different set of antibodies than the humoral). So this is good. This (and paxlovid) can help protect those remaining unprotected tissues of the upper respiratory that tend to be the first infected. It should be a good temporary mitigation until the USA and other countries approve of good intranasal sars-cov-2 vaccine boosters like India has (Innovac).

thatguy0900 3y ago
I honestly can't imagine taking more covid vaccines. I haven't even thought about covid for a year now.
- unsupp0rted 3y ago
  People with long covid have thought about it a lot during the last year
- QuantumGood 3y ago
  Some of us think 7 million dead is a lot, and find it harder to ignore than you do.
  - PraetorianGourd 3y ago
    3.4 million people die every year in the US. What makes these deaths acceptable but COVID a tragedy? And yes, many of those 3.4 million are preventable.
    - QuantumGood 3y ago
      It's fine if you want to make a point about COVID deaths—go ahead and say what you mean to say. I get there are many things to be said. But it's unclear why you're involving my comment with your soapbox. The parent comment to mine was about "not thinking about COVID". Why not just say what you mean to say in full? There is no need to try to put words into someone else's mouth to speak up for what you believe. You seem to simply be re-framing my comment in order to make yours. One way to start is along the lines of "This makes me think of an aspect of [the topic] which is [...] and what I think about that is [...]". (No one brought up or said any of those other deaths were acceptable. Nor did I say that COVID deaths were unacceptable or "tragic".)