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 is it surprising that reduced calorie intake in a default "sedentary" state may lead to immune or hormonal suppression, reproductive insufficiency, loss of bone density, and lean mass?
GLPs reduce your appetite and/or desire to eat, so you eat less, but you will still feel exhausted or drained because of a lack of energy.
Simply eating less is not the point; you are supposed to eat what your body needs and limit what it "wants." GLP drugs do not discriminate between nutritious, healthy intake and binge eating on fast foods you are trying to prevent.
GLPs don't do anything for that. The "metabolic boost" has not been proven to be anything beyond a 100 kcal increase in RMR. And most people claiming a boost cite an old study in which glucagon boosting RMR is simply an interpolation by the authors of the study.
A 100kcal RMR boost is less than 2 slices of bread equivalent, which is 130 kcal.
Being healthy is not just about not being fat; you can look at sumo wrestlers who hold considerable weight and whose health outcomes deteriorate once they go into retirement but keep the same diet.
It's highly likely a higher activity level is also needed along with body fat% reduction, while GLP users simply focus on reduced bodyweight.
Also, crashing your diet from a high GLP dose may result in bile or gallbladder issues down the line.
Few years from now, people will know pushing GLPs to the average guy who might be overweight by 10 or 20 kg is bad.
It takes only a 100 kcal surplus over a period of 4 years to add 20 kg of fat to your body, and 2 slices of bread = 130 kcal for comparison.
You don't need to eat a lot to get fat; become sedentary (which drops your lean mass, RMR, and reduced calorie burn from activities) = lower maintenance calories.
Now, eat 100 kcal in surplus for 4 years, and after 4 years, you are 20 kg overweight.
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
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.
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.
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
(I am not a medical doctor)
https://www.youtube.com/watch?v=yKPaVhpomks
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.
Otherwise, it's just a waste of our time.
Here you go (when it affects athletes, what makes anyone think that it will not affect sedentary people?): https://en.wikipedia.org/wiki/Relative_energy_deficiency_in_...
GLPs reduce your appetite and/or desire to eat, so you eat less, but you will still feel exhausted or drained because of a lack of energy.
Simply eating less is not the point; you are supposed to eat what your body needs and limit what it "wants." GLP drugs do not discriminate between nutritious, healthy intake and binge eating on fast foods you are trying to prevent.
GLPs don't do anything for that. The "metabolic boost" has not been proven to be anything beyond a 100 kcal increase in RMR. And most people claiming a boost cite an old study in which glucagon boosting RMR is simply an interpolation by the authors of the study.
A 100kcal RMR boost is less than 2 slices of bread equivalent, which is 130 kcal.
Being healthy is not just about not being fat; you can look at sumo wrestlers who hold considerable weight and whose health outcomes deteriorate once they go into retirement but keep the same diet.
It's highly likely a higher activity level is also needed along with body fat% reduction, while GLP users simply focus on reduced bodyweight.
Also, crashing your diet from a high GLP dose may result in bile or gallbladder issues down the line.
Few years from now, people will know pushing GLPs to the average guy who might be overweight by 10 or 20 kg is bad.
It takes only a 100 kcal surplus over a period of 4 years to add 20 kg of fat to your body, and 2 slices of bread = 130 kcal for comparison.
You don't need to eat a lot to get fat; become sedentary (which drops your lean mass, RMR, and reduced calorie burn from activities) = lower maintenance calories.
Now, eat 100 kcal in surplus for 4 years, and after 4 years, you are 20 kg overweight.
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.