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#glp#fat#body#less#immune#effect#lower#weight#between#probably

Discussion (40 Comments)Read Original on HackerNews

krupan3 minutes ago
Kind of kidding, but can we just put GLP-1s in the water supply already? So many benefits!
master_crababout 4 hours ago
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.

ramraj07about 3 hours 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.

nxobjectabout 2 hours 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

yayamoabout 3 hours 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.

joaopbnogueiraabout 3 hours ago
Or having a lower % of body fat (within healthy limits) is the factor improving a better immune response?
tptacekabout 3 hours ago
Generally studies showing off-target effects with GLP1s are at least attempting to control for this.
mathgeekabout 2 hours 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.
ryanchantsabout 3 hours ago
They are also anti-inflammatory, so it could be related to less systemic inflammation.
maxall4about 2 hours 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)

olalondeabout 2 hours 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

bitwizeabout 2 hours ago
Lower visceral fat as a percentage of body weight may bring benefits that are greater than proportional to total body mass lost.
DANmodeabout 1 hour 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.)

acheronabout 3 hours ago
Wow, bet they never thought of that. If only the researchers had thought to ask HN first.
clickety_clackabout 3 hours ago
Would you prefer that people accept claims uncritically? It’s a valid critique of the results.
wvenableabout 3 hours 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.

scheme27142 minutes ago
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.
tarxvfabout 3 hours ago
How expensive are GLP-1s again?
qginabout 1 hour ago
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.

dawnerdabout 1 hour ago
I’m paying 300/m out of pocket. Really wish my insurance covered it. It’s had a massively positive impact on life.
TehCorwizabout 2 hours ago
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.
drusepthabout 3 hours ago
> 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.
tptacekabout 3 hours ago
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.
jakevoytkoabout 2 hours ago
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
k12sosseabout 3 hours ago
Canada has generic semiglutide for under/around $300/mo depending on pharmacy
Scoundrellerabout 2 hours ago
More like CAD$90 for a 4mg pen
gavinrayabout 2 hours ago
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.

david-gpuabout 2 hours ago
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.
zug_zugabout 2 hours ago
For example?
oklahomasportsabout 3 hours ago
I’m just a customer. But Peptaura.com has GLPs 1-3 fr a few dollars a month
joshgachnangabout 3 hours ago
As low as $69/month through the compounding pharmacies.
astura23 minutes ago
Which pharmacy is that?
cromkaabout 2 hours ago
Inam betting it's because of lowered inflammation allowing for stronger immune response.
faangguyindiaabout 2 hours ago
This study is questionable because, where I live, TB is not a disease that happens to just anyone; it usually happens to people in poorly sanitized places with lower socioeconomic status. But pharma giants are going to publish ghost studies; they simply have too much money not to use it to further their drug empire.

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.

G3nD37 minutes ago
Your maintenance calories would rise as you gained weight. I don't think you're getting 20kg out of a fixed +100. I'm suspicious of a lot of your claims, but this really jumped out.