Using a large database of (deidentified) medical records, the researchers compared the outcomes of people taking a GLP-1 for their type 2 diabetes to people taking other common diabetes drugs between 2017 and 2025. GLP-1 users were significantly less likely to be diagnosed with TB for up to a five-year span, they found.
Both of these studies are observational and retrospective, meaning they can only show a correlation between GLP-1 use and reduced (or at least less severe) infections, not prove a direct cause-and-effect relationship. At the same time, these are the only latest pieces of evidence pointing to a genuine germ-busting benefit from GLP-1 drugs.
I wonder if the likelihood that people taking a GLP-1 are probably better off financially, have a health care provider willing to spend on the drugs (and therefore probably a better medical system) or a combination of these and other traits are the real reason there are fewer infections.
They use a method called propensity score matching to try their best to match patients on both sides using a simple linear model with various features that try to ensure that only pairs of closely matched patient histories are compared.
Unfortunately this is rarely clean. Its also easy to make mistakes. Sometimes two arms are fundamentally incomparable. The quality and rigor of the comparison is often determined by a lot of extra checks and validations, and different journals demand different levels of rigor. I need to read it carefully to judge if this is good or not.
It looks like both do standard individual covariate checks for post-match balance, with SMDs. I'm surprised they haven't assessed balance for at least pairwise interactions, too -- we should be balancing out joint risk factors too, no?
I haven't worked on these designs, but I remember the methodologist that taught me this in grad school giving us a lecture about this.
EDIT: the BMJ article (laudably) provides access to the analyis code, although I won't have time to review it:
They already do acknowledge socioeconomic (and other confounding factors) in the analysis.
The primary analysis they perform is a ‘Propensity Score Match’ which is a technique used specifically to address for confounders in observational studies, and they do report balanced cohorts.
Still they write in their discussion “Although we adjus-
ted for several available proxies of socioeconomic and lifestyle status,
direct measures of income, insurance coverage, or out-of-pocket
payment were not available in the TriNetX database. Residual confounding related to unmeasured socioeconomic factors, therefore,
cannot be excluded“
Given the size of the dataset, the effect size, significance and sensitivity testing they did I think it’s very strong evidence for GLP1s causing this and it would be very very surprising to me to see the effect disappear even if they had perfect socioeconomic data.
With so many signs of improvement, even if some of them happens to be just flukes, from so many different areas, it feels like a penicillin moment. And i suppose penicillin also was initially mostly available to the ones with better socio-economy.
I’m sure you can just look up the studies, but note that GLP1s are widely prescribed to people without weight issues —— weight loss itself was originally an off-target effect. I have friends who run marathons who are on semaglutide.
This video by a medical doctor cites many studies showing that GLP-1 health benefits go beyond weight loss (see video description for link to papers): https://www.youtube.com/watch?v=yKPaVhpomks
The benefit is probably from the removal of fat, not a direct antibacterial/antiviral effect. Fat plays a complex immunoregulatory role in human physiology: it down-regulates some pathways, while up-regulating others (notoriously, the production of IL6 is carried out, in part, by adipocytes). The overall effect of fat on the immune system, however, is negative: it tends to increase the chances of rheumatological disorders, cancers, and many other diseases. Alternatively, the effect may be due to some sociological factor that their analysis failed to account for.
Nobody's denying this, but the interesting story about GLP-1s is that after you control for fat loss (for instance, by taking cohorts of patients that aren't losing weight) you still get evidence of these off-target effects.
That's true, and it's also one of those factoids that everybody already knows but certain people can't help themselves from bringing up every time it's even tenuously relevant.
The fact that it was the top comment only shows that people agreed or liked it, not that it was actually valuable, accurate, or useful. Popularity and value aren't the same thing, correlation is not causation, etc, etc...
Most observational studies do in fact account for the first thing a random HN poster can come up with 5 seconds after reading the title. So there is very little value in such a comment.
This was published in Nature, I'm pretty sure the reviewers understand and account for that. HN and reasonably educated people always think this is some huge gotcha, second only to "CORRELATION != CAUSATION!!!!"
Nature isn't an arbiter of truth, it's a publisher of papers. It's also meant to be read critically by people who see a paper like this and and think "interesting, but this is just an observational study, I'd like to see more research, maybe something with more controls before I believe this".
Say what you want about the "correlation doesn't imply causation", but many people do not understand why that is. As a shorthand for "hey, you don't know the statistics behind this, so don't take the pretty picture at face value", it's pretty good.
I would imagine people going out of their way to take GLP-1 might also lose weight, be more active, and be also likely to eat better. Which I imagine would have a large effect on "germ busting"
Question for people using GLP-1s: Do you plan to stay on them indefinitely? Are you concerned about gaining back the weight if you ever stop taking them?
I've had success with weight loss through diet and exercise (exclusive and inclusive at different points) but had trouble keeping it off. GLP-1s are attractive for sure but I cannot make up my mind on if it's worth the risks (both known and unknown). I know everything has risks, including lots of risks about being overweight and maybe keeping the weight off is an easier problem for a healthier version of myself after using a GLP-1. I don't know.
I hike 5 miles a day, I ate super-healthy (no ultra-processed foods, cook at home every day etc), only drink water, coffee & tea. Actually rarely eat stuff which has added sugar on the package, and avoid foods that have > 5 ingredients (more means it's too processed for me). I bake my own bread (sourdough, salt, flour, water, maybe home-grown japalenos).
And yet, I kept on gaining weight...
My problem is don't get the signal that I'm full fast enough. I have tried _everything_. Drink 2 glasses of water, fibers, eat slower, smaller plates, dietician, track calories.
They work in isolation, but I always end up hungry. Compare it to alcohol. The desire to drink. The solution there is easy. No more alcohol, and that works for most people.
With food? Can't completely abstain...
Went on GLP-1, worked great. Because of hip surgery had to stop for a while, and the weight just came back, because naturally, you revert to your old eating habits, as you chase the signal of satiation.
Now back on them and I'll be on it until the day I die. I pay $450 a month for now because insurance doesn't think I am fat enough now (I'm not). They expect me to go back to my overweight weight..., and even then, acceptance is not guaranteed.
In terms of risks: If I don't take it I'll wear out my knees sooner (hips were related to genetics, not weight). If I don't take it I need 1h more / sleep every night, I have sleep apnea, higher blood pressure, higher cholesterol (doesn't mater how healthy EVOO is, if you eat a huge salad you'll eat a lot of oil).
It's not a risk of GLP-1 against nothing. It's GLP-1 risks vs heart-disease/etc.
That's a known fact. That's why the first thing doctors say to overweight people is to lose weight for pretty much any disease. Some get hurt and blame the doctors, which doesn't help them.
Could be due to better control of blood sugar. E.g. lower blood sugar increases inflammation, decrease immune response and provides bacteria a readily available source of food.
I self pay for one from lilly-direct for about $200/mo. Insurance doesn't cover any part of it yet. It required a prescription from my doc and it comes in the mail.
Are you sure that it is not 30mg total per vial, with $100 being the price for 10 vials? Because this stuff comes in powder form, not in liquid form, so mg/mL is an odd unit of measurement. Perhaps I misunderstand your comment.
It's 30mg per vial. In addition to that being the going rate for 300mg total...the calculations and final price for 20 weeks match up to 300mg total, not 300mg per vial.
> GLP-1 receptor agonist medications typically cost between $149 and $350 per month for cash-pay oral pills, and $900 to $1,400+ per month for list-price injectables without insurance.
I don't know that anyone really pays list price for injectables, because the vendors do discount programs. Without insurance coverage, tirzepetide via Amazon Pharmacy is something like $450/mo.
Yeah this is what I pay for Zepbound through LillyDirect. I also eat less food and drink less alcohol than I used to. So the net loss is probably smaller, maybe $200/mo
I think you're right I confused wegovy prices with generics. Thank you for clarifying. I'm new to it and will find out about pricing very soon - my provider dropped covering the medication (the day I submitted for pre-approval) -because it worked so well it became popular :P
I pay $450 a month out of pocket and that is with a coupon, it used to be $1200 a month. It's worth it to me, it's life-changing. My bp went down from dangerous levels to normal.
I was at a hepatology meeting focussed on fatty liver a couple of years ago, where a well regarded head of hepatology at a major national quarternary referral centre, joked that we should be putting this in the water supply...
i can kinda get how a glp-1 can be a miracle drug for weight: if we assume that simple molecular fixes to problems will eventually be found by evolution, then when we change our environment rapidly (e.g., with cheap bountiful calories) then this presents an opportunity for a miracle drug, since evolution will take some time to find the fix.
but for something like reducing disease infection, i find it a lot harder to understand why we don't create this naturally unless there is some equal-but-opposite cost that we'd incur, or if there is not actually as big of a benefit as we believe (or if this is all just colinear with the weight loss stuff).
note: i have no background in any of this and have no idea what i'm talking about
I'm not a doctor or biologist, but remember that bacteria is a far simpler organism with a much shorter individual lifespan than a human. Depending on the species and their environment, they might divide every 12 minutes or every 24 hours. A new human generation will be more 15 to 35 years. Their reproduction is also simpler. Genes are inherited or mutated mostly at the time of reproduction. Selection is mostly therefore over the course of generations.
These things together mean their microevolution is on a different timescale than ours.
> Using a large database of (deidentified) medical records, the researchers compared the outcomes of people taking a GLP-1 for their type 2 diabetes to people taking other common diabetes drugs between 2017 and 2025. GLP-1 users were significantly less likely to be diagnosed with TB for up to a five-year span, they found.
This is incredibly manipulative. So, we're going to ignore all other factors that may have played into this and just assume it was due directly to GLP-1 use?
You read reporting about a study, made assumptions that it was bad, and posted your opinion without actually reading the study to see whether the scientists involved were smart enough to try to rule out other factors.
I read a news report on the study that was linked, yes. But my issue isn't with the researchers/their process, it's with how this is presented in the headline vs. what the actual reason was backing the claim.
There's nothing to "do better" about; you just don't like my opinion (and that's perfectly fine).
Yes, p-hacking happens, incentives in academia are increasingly misaligned etc, but I assume that there are competent people and systems to avoid such obvious issues? It's science 101 to avoid spurious correlations. Sure there might be some tricky ones, but if the's obvious one that came to your mind, very good chance it's been accounted for.
Using a large database of (deidentified) medical records, the researchers compared the outcomes of people taking a GLP-1 for their type 2 diabetes to people taking other common diabetes drugs between 2017 and 2025. GLP-1 users were significantly less likely to be diagnosed with TB for up to a five-year span, they found.
Both of these studies are observational and retrospective, meaning they can only show a correlation between GLP-1 use and reduced (or at least less severe) infections, not prove a direct cause-and-effect relationship. At the same time, these are the only latest pieces of evidence pointing to a genuine germ-busting benefit from GLP-1 drugs.
I wonder if the likelihood that people taking a GLP-1 are probably better off financially, have a health care provider willing to spend on the drugs (and therefore probably a better medical system) or a combination of these and other traits are the real reason there are fewer infections.
They use a method called propensity score matching to try their best to match patients on both sides using a simple linear model with various features that try to ensure that only pairs of closely matched patient histories are compared.
Unfortunately this is rarely clean. Its also easy to make mistakes. Sometimes two arms are fundamentally incomparable. The quality and rigor of the comparison is often determined by a lot of extra checks and validations, and different journals demand different levels of rigor. I need to read it carefully to judge if this is good or not.
It looks like both do standard individual covariate checks for post-match balance, with SMDs. I'm surprised they haven't assessed balance for at least pairwise interactions, too -- we should be balancing out joint risk factors too, no?
I haven't worked on these designs, but I remember the methodologist that taught me this in grad school giving us a lecture about this.
EDIT: the BMJ article (laudably) provides access to the analyis code, although I won't have time to review it:
github.com/nilskruger/Tirzepatide-and-the-Risk-of-Atherosclerotic-Cardiovascular-Events
They already do acknowledge socioeconomic (and other confounding factors) in the analysis. The primary analysis they perform is a ‘Propensity Score Match’ which is a technique used specifically to address for confounders in observational studies, and they do report balanced cohorts. Still they write in their discussion “Although we adjus- ted for several available proxies of socioeconomic and lifestyle status, direct measures of income, insurance coverage, or out-of-pocket payment were not available in the TriNetX database. Residual confounding related to unmeasured socioeconomic factors, therefore, cannot be excluded“
Given the size of the dataset, the effect size, significance and sensitivity testing they did I think it’s very strong evidence for GLP1s causing this and it would be very very surprising to me to see the effect disappear even if they had perfect socioeconomic data.
With so many signs of improvement, even if some of them happens to be just flukes, from so many different areas, it feels like a penicillin moment. And i suppose penicillin also was initially mostly available to the ones with better socio-economy.
Or having a lower % of body fat (within healthy limits) is the factor improving a better immune response?
Generally studies showing off-target effects with GLP1s are at least attempting to control for this.
I’d be interested to see the data for that claim, since I would imagine a strong correlation between glp use and lower body fat.
I’m sure you can just look up the studies, but note that GLP1s are widely prescribed to people without weight issues —— weight loss itself was originally an off-target effect. I have friends who run marathons who are on semaglutide.
Because they need to medically or it helps athletically ?
Because they need it medically.
This video by a medical doctor cites many studies showing that GLP-1 health benefits go beyond weight loss (see video description for link to papers): https://www.youtube.com/watch?v=yKPaVhpomks
It may be that those without repeated toxic caloric exposure allows the immune system to focus on other aspects.
> toxic caloric exposure
Is that a thing?
The benefit is probably from the removal of fat, not a direct antibacterial/antiviral effect. Fat plays a complex immunoregulatory role in human physiology: it down-regulates some pathways, while up-regulating others (notoriously, the production of IL6 is carried out, in part, by adipocytes). The overall effect of fat on the immune system, however, is negative: it tends to increase the chances of rheumatological disorders, cancers, and many other diseases. Alternatively, the effect may be due to some sociological factor that their analysis failed to account for.
(I am not a medical doctor)
Many of the health benefits, including cardiovascular and kidney health, have been shown to go beyond or be unrelated to changes in body weight.
https://www.youtube.com/watch?v=yKPaVhpomks
Lower visceral fat as a percentage of body weight may bring benefits that are greater than proportional to total body mass lost.
Nobody's denying this, but the interesting story about GLP-1s is that after you control for fat loss (for instance, by taking cohorts of patients that aren't losing weight) you still get evidence of these off-target effects.
How much of “fat” also includes biofilmed infection stifling your electrical system and indeed signaling your immune system to not work as well?
(You can look this up regarding biofilms, I just did today.)
Then you must have some links available
They are also anti-inflammatory, so it could be related to less systemic inflammation.
Wow, bet they never thought of that. If only the researchers had thought to ask HN first.
Would you prefer that people accept claims uncritically? It’s a valid critique of the results.
If the commenter read the study and found that they did not, in fact, account for that then it would be valid to point it out here.
Otherwise, it's just a waste of our time.
By its fundamental design, an observational study cannot account for everything. That is the critique and it is a valid one.
That's true, and it's also one of those factoids that everybody already knows but certain people can't help themselves from bringing up every time it's even tenuously relevant.
It might be common sense if you work with statistics, but most people don’t, and the only way they would know these things is if someone says them.
Regardless, it was the top comment so people clearly think it was valuable enough to vote for.
The fact that it was the top comment only shows that people agreed or liked it, not that it was actually valuable, accurate, or useful. Popularity and value aren't the same thing, correlation is not causation, etc, etc...
Most observational studies do in fact account for the first thing a random HN poster can come up with 5 seconds after reading the title. So there is very little value in such a comment.
This was published in Nature, I'm pretty sure the reviewers understand and account for that. HN and reasonably educated people always think this is some huge gotcha, second only to "CORRELATION != CAUSATION!!!!"
Nature isn't an arbiter of truth, it's a publisher of papers. It's also meant to be read critically by people who see a paper like this and and think "interesting, but this is just an observational study, I'd like to see more research, maybe something with more controls before I believe this".
Say what you want about the "correlation doesn't imply causation", but many people do not understand why that is. As a shorthand for "hey, you don't know the statistics behind this, so don't take the pretty picture at face value", it's pretty good.
I would imagine people going out of their way to take GLP-1 might also lose weight, be more active, and be also likely to eat better. Which I imagine would have a large effect on "germ busting"
Question for people using GLP-1s: Do you plan to stay on them indefinitely? Are you concerned about gaining back the weight if you ever stop taking them?
I've had success with weight loss through diet and exercise (exclusive and inclusive at different points) but had trouble keeping it off. GLP-1s are attractive for sure but I cannot make up my mind on if it's worth the risks (both known and unknown). I know everything has risks, including lots of risks about being overweight and maybe keeping the weight off is an easier problem for a healthier version of myself after using a GLP-1. I don't know.
They cured my migraines, dose small enough to be stable weight. But I have my life back, I get tired instead of getting migraines now.
Half the smallest dose, keeps my headaches away for 2-3 weeks. My food intake simply changed, I got used to eating less / healthier.
Yes.
I hike 5 miles a day, I ate super-healthy (no ultra-processed foods, cook at home every day etc), only drink water, coffee & tea. Actually rarely eat stuff which has added sugar on the package, and avoid foods that have > 5 ingredients (more means it's too processed for me). I bake my own bread (sourdough, salt, flour, water, maybe home-grown japalenos).
And yet, I kept on gaining weight...
My problem is don't get the signal that I'm full fast enough. I have tried _everything_. Drink 2 glasses of water, fibers, eat slower, smaller plates, dietician, track calories.
They work in isolation, but I always end up hungry. Compare it to alcohol. The desire to drink. The solution there is easy. No more alcohol, and that works for most people.
With food? Can't completely abstain...
Went on GLP-1, worked great. Because of hip surgery had to stop for a while, and the weight just came back, because naturally, you revert to your old eating habits, as you chase the signal of satiation.
Now back on them and I'll be on it until the day I die. I pay $450 a month for now because insurance doesn't think I am fat enough now (I'm not). They expect me to go back to my overweight weight..., and even then, acceptance is not guaranteed.
In terms of risks: If I don't take it I'll wear out my knees sooner (hips were related to genetics, not weight). If I don't take it I need 1h more / sleep every night, I have sleep apnea, higher blood pressure, higher cholesterol (doesn't mater how healthy EVOO is, if you eat a huge salad you'll eat a lot of oil).
It's not a risk of GLP-1 against nothing. It's GLP-1 risks vs heart-disease/etc.
At least with GLP-1 I get to live now.
Thank you, I really appreciate your response.
Maybe being overweight is bad for the immune system
It is well known that you have higher levels of inflammation if overweight, which generally worsens your immune response.
huge if true
That's a known fact. That's why the first thing doctors say to overweight people is to lose weight for pretty much any disease. Some get hurt and blame the doctors, which doesn't help them.
Could be due to better control of blood sugar. E.g. lower blood sugar increases inflammation, decrease immune response and provides bacteria a readily available source of food.
> lower blood sugar increases inflammation
This is backwards. I think you mean HIGHER blood sugar, right?
How expensive are GLP-1s again?
AU$140 (~US$100) per 4mg, which is approx one month, here.
AU$25 (~US$18), or AU$7.70 (~US$5.50) with a concession card if you qualify for subsidy.
If you're in Australia it's worth a chat with your GP rather than less regulated channels.
I self pay for one from lilly-direct for about $200/mo. Insurance doesn't cover any part of it yet. It required a prescription from my doc and it comes in the mail.
Depends on how much assurance you need that you're actually injecting what you think you’re injecting.
If you’re okay with just being probably sure, the price is a lot lower.
Yup, plus my GLP-1 dealer promises that if it kills me, I won’t have to pay. Really no downside.
I’m paying 300/m out of pocket. Really wish my insurance covered it. It’s had a massively positive impact on life.
How technical do you want to get?
The grey-market price from China, is about $100 for 10 x (30mg/mL, 10mL) vials of Tirzepatide. Semaglutide is cheaper.
At the highest dose of 15mg/wk, that's 20 weeks for $100.
Are you sure that it is not 30mg total per vial, with $100 being the price for 10 vials? Because this stuff comes in powder form, not in liquid form, so mg/mL is an odd unit of measurement. Perhaps I misunderstand your comment.
It's 30mg per vial. In addition to that being the going rate for 300mg total...the calculations and final price for 20 weeks match up to 300mg total, not 300mg per vial.
For example?
> GLP-1 receptor agonist medications typically cost between $149 and $350 per month for cash-pay oral pills, and $900 to $1,400+ per month for list-price injectables without insurance.
I don't know that anyone really pays list price for injectables, because the vendors do discount programs. Without insurance coverage, tirzepetide via Amazon Pharmacy is something like $450/mo.
Yeah this is what I pay for Zepbound through LillyDirect. I also eat less food and drink less alcohol than I used to. So the net loss is probably smaller, maybe $200/mo
Canada has generic semiglutide for under/around $300/mo depending on pharmacy
More like CAD$90 for a 4mg pen
I think you're right I confused wegovy prices with generics. Thank you for clarifying. I'm new to it and will find out about pricing very soon - my provider dropped covering the medication (the day I submitted for pre-approval) -because it worked so well it became popular :P
I pay $450 a month out of pocket and that is with a coupon, it used to be $1200 a month. It's worth it to me, it's life-changing. My bp went down from dangerous levels to normal.
I’m just a customer. But Peptaura.com has GLPs 1-3 fr a few dollars a month
Here in Canada, a generic semaglutide injection is $104(CAD) / month
As low as $69/month through the compounding pharmacies.
Which pharmacy is that?
I was at a hepatology meeting focussed on fatty liver a couple of years ago, where a well regarded head of hepatology at a major national quarternary referral centre, joked that we should be putting this in the water supply...
> we should be putting this in the water supply...
Talked to a physician last year who said the entire planet should be on GLP-1s.
Inam betting it's because of lowered inflammation allowing for stronger immune response.
i can kinda get how a glp-1 can be a miracle drug for weight: if we assume that simple molecular fixes to problems will eventually be found by evolution, then when we change our environment rapidly (e.g., with cheap bountiful calories) then this presents an opportunity for a miracle drug, since evolution will take some time to find the fix.
but for something like reducing disease infection, i find it a lot harder to understand why we don't create this naturally unless there is some equal-but-opposite cost that we'd incur, or if there is not actually as big of a benefit as we believe (or if this is all just colinear with the weight loss stuff).
note: i have no background in any of this and have no idea what i'm talking about
I'm not a doctor or biologist, but remember that bacteria is a far simpler organism with a much shorter individual lifespan than a human. Depending on the species and their environment, they might divide every 12 minutes or every 24 hours. A new human generation will be more 15 to 35 years. Their reproduction is also simpler. Genes are inherited or mutated mostly at the time of reproduction. Selection is mostly therefore over the course of generations.
These things together mean their microevolution is on a different timescale than ours.
Kind of kidding, but can we just put GLP-1s in the water supply already? So many benefits!
> Using a large database of (deidentified) medical records, the researchers compared the outcomes of people taking a GLP-1 for their type 2 diabetes to people taking other common diabetes drugs between 2017 and 2025. GLP-1 users were significantly less likely to be diagnosed with TB for up to a five-year span, they found.
This is incredibly manipulative. So, we're going to ignore all other factors that may have played into this and just assume it was due directly to GLP-1 use?
You read reporting about a study, made assumptions that it was bad, and posted your opinion without actually reading the study to see whether the scientists involved were smart enough to try to rule out other factors.
I've done this myself, but we should do better.
I read a news report on the study that was linked, yes. But my issue isn't with the researchers/their process, it's with how this is presented in the headline vs. what the actual reason was backing the claim.
There's nothing to "do better" about; you just don't like my opinion (and that's perfectly fine).
Yes, p-hacking happens, incentives in academia are increasingly misaligned etc, but I assume that there are competent people and systems to avoid such obvious issues? It's science 101 to avoid spurious correlations. Sure there might be some tricky ones, but if the's obvious one that came to your mind, very good chance it's been accounted for.