6 ms·

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 tak

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.

joaopbnogueira 13d ago
Or having a lower % of body fat (within healthy limits) is the factor improving a better immune response?
- Ecko123 13d ago
  [dead]
- tptacek 13d ago
  Generally studies showing off-target effects with GLP1s are at least attempting to control for this.
  - mathgeek 13d ago
    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.
    - tptacek 13d ago
      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.
      - Melatonic 13d ago
        Because they need to medically or it helps athletically ?
        tptacek 12d ago
        Because they need it medically.
    - olalonde 13d ago
      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 https://www.youtube.com/watch?v=yKPaVhpomks
- snovv_crash 13d ago
  It may be that those without repeated toxic caloric exposure allows the immune system to focus on other aspects.
  - relaxing 13d ago
    > toxic caloric exposure Is that a thing?
ryanchants 13d ago
They are also anti-inflammatory, so it could be related to less systemic inflammation.
ramraj07 13d ago
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.
- nxobject 13d ago
  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
yayamo 13d ago
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.
- trhway 13d ago
  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.
acheron 13d ago
Wow, bet they never thought of that. If only the researchers had thought to ask HN first.
- clickety_clack 13d ago
  Would you prefer that people accept claims uncritically? It’s a valid critique of the results.
  - wvenable 13d ago
    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.
    - clickety_clack 13d ago
      By its fundamental design, an observational study cannot account for everything. That is the critique and it is a valid one.
      - wvenable 13d ago
        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.
      - j4yav 13d ago
        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.
        clickety_clack 12d ago
        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.
maxall4 13d ago
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)
- olalonde 13d ago
  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 https://www.youtube.com/watch?v=yKPaVhpomks
  - bitwize 13d ago
    Lower visceral fat as a percentage of body weight may bring benefits that are greater than proportional to total body mass lost.
    - tptacek 13d ago
      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.
- DANmode 13d ago
  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.)
  - cousinbryce 12d ago
Melatonic 13d ago
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"

joaopbnogueira 13d ago

Or having a lower % of body fat (within healthy limits) is the factor improving a better immune response?

Ecko123 13d ago
[dead]
tptacek 13d ago
Generally studies showing off-target effects with GLP1s are at least attempting to control for this.
- mathgeek 13d ago
  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.
  - tptacek 13d ago
    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.
    - Melatonic 13d ago
      Because they need to medically or it helps athletically ?
      - tptacek 12d ago
        Because they need it medically.
  - olalonde 13d ago
    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 https://www.youtube.com/watch?v=yKPaVhpomks
snovv_crash 13d ago
It may be that those without repeated toxic caloric exposure allows the immune system to focus on other aspects.
- relaxing 13d ago
  > toxic caloric exposure Is that a thing?

ryanchants 13d ago

They are also anti-inflammatory, so it could be related to less systemic inflammation.

ramraj07 13d ago

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.

nxobject 13d ago
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

yayamo 13d ago

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.

trhway 13d ago
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.

acheron 13d ago

Wow, bet they never thought of that. If only the researchers had thought to ask HN first.

clickety_clack 13d ago
Would you prefer that people accept claims uncritically? It’s a valid critique of the results.
- wvenable 13d ago
  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.
  - clickety_clack 13d ago
    By its fundamental design, an observational study cannot account for everything. That is the critique and it is a valid one.
    - wvenable 13d ago
      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.
    - j4yav 13d ago
      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.
      - clickety_clack 12d ago
        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.

maxall4 13d ago

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)

olalonde 13d ago
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 https://www.youtube.com/watch?v=yKPaVhpomks
- bitwize 13d ago
  Lower visceral fat as a percentage of body weight may bring benefits that are greater than proportional to total body mass lost.
  - tptacek 13d ago
    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.
DANmode 13d ago
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.)
- cousinbryce 12d ago

Melatonic 13d ago

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"