GLP-1s are being linked to fewer serious infections, including TB

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.

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?

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

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)

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

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"

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.

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.

It is well known that you have higher levels of inflammation if overweight, which generally worsens your immune response.

huge if true

> lower blood sugar increases inflammation

This is backwards. I think you mean HIGHER blood sugar, right?

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.

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.

I’m paying 300/m out of pocket. Really wish my insurance covered it. It’s had a massively positive impact on life.

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.

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.

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.

> 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’m just a customer. But Peptaura.com has GLPs 1-3 fr a few dollars a month

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.

Here in Canada, a generic semaglutide injection is $104(CAD) / month

As low as $69/month through the compounding pharmacies.

> 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.

[dead]

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.

"GLP medications blunt your appetite so you eat less, but you still end up feeling completely drained because your body lacks fuel."

How many people report that? Not that many, AFAIK.

"GLP drugs cannot distinguish between nutrient-dense meals and the junk food binges you are trying to avoid."

This again goes against what people report - aversion to junk food so strong that McDonalds et al. consider this a potential threat to their business model.

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.

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.