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:
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.
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.
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
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.
Why are people surprised that severely cutting calories while staying sedentary
trashes the immune system, disrupts hormones, impairs reproductive function, and
strips away bone density and muscle?
If this happens to high-performing athletes, there is no reason to believe
sedentary folks are immune. The research behind Relative Energy Deficiency in
Sport breaks down these exact mechanisms:
https://en.wikipedia.org/wiki/Relative_energy_deficiency_in_...
GLP medications blunt your appetite so you eat less, but you still end up
feeling completely drained because your body lacks fuel. The goal should never
be just blindly slashing calories. You have to feed your body what it needs
rather than solely cutting what it craves, and GLP drugs cannot distinguish
between nutrient-dense meals and the junk food binges you are trying to avoid.
They do not fix metabolism, either. Any claimed "metabolic boost" has never been
proven beyond a minor 100 kcal increase in resting metabolic rate (RMR). Most
people pushing that claim rely on an older study where glucagon raising RMR was
merely an interpolation by the authors. To put that in perspective, a 100 kcal
bump is less than two slices of bread, which sit around 130 kcal.
Being healthy is not just about avoiding excess body fat. Look at retired sumo
wrestlers: they carry significant weight, yet their health markers crater once
they stop training while keeping their diet identical. Real body fat reduction
requires higher activity levels, but most GLP users fixate entirely on scale
weight. Crashing your intake on high doses also sets you up for serious bile and
gallbladder complications down the road.
Give it a few years, and we will look back on handing GLP prescriptions to
people who are only 10 to 20 kg overweight as a major mistake. You do not have
to gorge yourself to gain weight. Dropping into a sedentary lifestyle reduces
muscle mass, lowers your RMR, and tanks your daily energy expenditure, pulling
your maintenance baseline down with it. Once your maintenance drops, running a
tiny surplus of just 100 kcal a day for four years will easily pack on 20 kg of
fat.
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.
> 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
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.
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
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.
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.
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.
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
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.
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.
Inam betting it's because of lowered inflammation allowing for stronger immune response.
Why are people surprised that severely cutting calories while staying sedentary trashes the immune system, disrupts hormones, impairs reproductive function, and strips away bone density and muscle?
If this happens to high-performing athletes, there is no reason to believe sedentary folks are immune. The research behind Relative Energy Deficiency in Sport breaks down these exact mechanisms: https://en.wikipedia.org/wiki/Relative_energy_deficiency_in_...
GLP medications blunt your appetite so you eat less, but you still end up feeling completely drained because your body lacks fuel. The goal should never be just blindly slashing calories. You have to feed your body what it needs rather than solely cutting what it craves, and GLP drugs cannot distinguish between nutrient-dense meals and the junk food binges you are trying to avoid.
They do not fix metabolism, either. Any claimed "metabolic boost" has never been proven beyond a minor 100 kcal increase in resting metabolic rate (RMR). Most people pushing that claim rely on an older study where glucagon raising RMR was merely an interpolation by the authors. To put that in perspective, a 100 kcal bump is less than two slices of bread, which sit around 130 kcal.
Being healthy is not just about avoiding excess body fat. Look at retired sumo wrestlers: they carry significant weight, yet their health markers crater once they stop training while keeping their diet identical. Real body fat reduction requires higher activity levels, but most GLP users fixate entirely on scale weight. Crashing your intake on high doses also sets you up for serious bile and gallbladder complications down the road.
Give it a few years, and we will look back on handing GLP prescriptions to people who are only 10 to 20 kg overweight as a major mistake. You do not have to gorge yourself to gain weight. Dropping into a sedentary lifestyle reduces muscle mass, lowers your RMR, and tanks your daily energy expenditure, pulling your maintenance baseline down with it. Once your maintenance drops, running a tiny surplus of just 100 kcal a day for four years will easily pack on 20 kg of fat.
How expensive are GLP-1s again?
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.
> 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
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.
For example?
I’m just a customer. But Peptaura.com has GLPs 1-3 fr a few dollars a month
As low as $69/month through the compounding pharmacies.