back
151 comments
At what point do we start to re-evaluate and re-test old assumptions about how much weight/caloric restriction impacts things? It seems unlikely that a molecule that slots into receptors in the pancreas also does something(?) to cardiac muscle [1], addiction [2], and now osteoarthritis(!).

This feels like a stretch to say that this happens independent of weight loss, and much more like we may have underestimated the impacts of weight loss on all of these other facets of life.

[1] - https://pmc.ncbi.nlm.nih.gov/articles/PMC12431743/

[2] - https://med.stanford.edu/news/insights/2025/04/ozempic-addic...

Similar reports have been ongoing about Metformin (another medication used for diabetes that causes weight loss and improves metabolic profile).

It's the simplest explanation that we have been underestimating just how unhealthy we are?

There's a synergy here, eat healthier, reduce blood sugar spikes, lose weight. And you are healthier than each individual effect alone would cause.

Maybe we're just ruining our bodies even if we don't put on weight by eating sugary foods that spoke our blood sugar. Or big meals that constantly make us switch into sit down and digest mode.

I'm open to something more happening but this isn't just GLPs. It seems we have uniquely attacked our bodies in a way that diabetes is the ultimate result but the entire journey is exquisitely toxic to our physiology.

Maybe fasting helps. Maybe keto helps. But this is similar to people who live off McDonalds suddenly go vegan and become healthy, is veganism that great? Or was the alternative for you just so awful for you?

FTFA:

> By designing a precise diet-controlled setting to rule out the effect of appetite suppression and weight loss induced by SG, we demonstrate a weight loss-independent mechanism.

Hormones do a lot all over your body.

You're commenting on a paper that specifically found OA improvement without weight loss improvement...

> addition [2]

I had heard about the effects on addiction but this typo had me thinking there might be some effect on arithmetic ability, too.

Why is that unlikely?

There are other known molecules that are many to many like cortisol, testosterone, and insulin.

There's GLP-1 receptors in the brain, they induce neurogenesis
If they're not losing weight they're not restricting calories. Energy has to come from somewhere.

They explicitly controlled for all of this.

I mean...if you read the paper they control for that.
Independent of weight loss, semaglutide (Ozempic) improves knee osteoarthritis by cartilage restoration, in both the mouse model and a small randomized clinical trial.

Old thinking was the benefit of GLP-1 drugs (like Ozempic) was solely from weight loss, however studies are showing there are other unique benefits. It's probably that semaglutide reduces inflammation allowing the body to repair and improves mitochondrial function in cartilage cells.

One thing I have noticed on Mounjaro is a (at least subjectively) significant decrease in impulse spending / buying random crap off Amazon. I have ADHD and that has been a real problem for quite a while - even with ADHD medication (Elvanse/Vyvanse in my case).

The part of Mounjaro that regulates the craving side of the weight loss equation (like reducing 'food noise' and the desire for sugary and fatty foods) seems to also affect other behaviors due to Mounjaro's effect on the brain's reward circuitry. I believe there are also early preliminary studies that indicate it can help with addictions like alcoholism.

Those drugs really are quite something. Shame they're so damn expensive. Insurance here in Germany is unfortunately legally prohibited from covering GLP-1 class drugs for weight loss unless you have a diabetes diagnosis.

Seems like a wonder drug to me. The benefits just keep piling up.

Where I live (Sweden), there's a perhaps surprisingly large portion of overweight/obesese people, especially in the countryside. Semaglutide could really do wonders here for quality of life and health.

Meanwhile, the newspapers keep pushing exceptional scare stories. The one that stuck with me from a few weeks ago went like 'I puked up my own poop.' Perhaps tellingly, the people they tend to feature in these stories typically aren't really overweight.

It is not yet generally subsidized, unless you have a diabetes type 2 diagnose. It really should be, above some BMI (sans body builders).

My psychiatrist is really interested in how it affects anxiety and depression as he has now seena number of improvements from a bunch of patients (including myself) who use the drug. Im on meds for both and only after i started on monjourno did i feel a signifigant change. The food cravings gone due to the nuerological effects but the stress levels lower as it seems to be impacting seratonin levels in ways as you increase dose.
The most surprising effect of Mounjaro, at least initially was that it drastically reduced by desire to drink beer, and when I started, my drinking was at a very unhealthy level (beer calories being a major factor in my weight problem). But maybe I'm an odd case, as I had a real beer habit but don't like wine and very rarely touched spirits.

Actually losing some weight as well as cutting my drinking down, helped me with depression far more than SSRIs (which had previously led to even faster weight gain)

Unfortunately, the effects started to diminish somewhat after about a year on it, as if I was building up a bit of a tolerance to the drug. And then I switched to Wegovy (=Ozempic) after big UK price hikes to Mounjaro, and found it much less effective, started gaining weight again (winter/xmas didn't help). Switching back to Mounjaro at the moment, but having to slowly step back up from a lower dose. Not expecting to see the initial near-miraculous effects again, expecting to have to combine it with some actual willpower and more exercise going forwards.

> a number of improvements from a bunch of patients (including myself) who use the drug.

Does that include people who haven't lost weight on the drug? I imagine a lot of people will start to feel better when they look better and are healthier.

Semaglutide has a warning about not being suitable for folks with depression. I don't think I've seen any changes to my moods. I'm type-II bipolar and if anything my depression episodes are slightly worse now.
If you don't mind sharing, at what dose did you see positive impact on mood?
If it can somehow restore spinal disc function, I'm gonna start snorting the stuff.
I had a bulging lumbar disc - pure agony for 18 months. I had become used to carrying a lumbar pillow around with me everywhere I went. I couldn't lean forward for more than about 30 seconds without it being unbearable.

Then someone suggested I try dead hangs, stretching my hamstrings, and really cranking the McKenzie stretch. I'm not sure which one made the difference (all 3?), but pain was gone in 2 weeks.

Maybe it will help, maybe it won't. But since someone took a flyer telling me, I always share this with others in the small chance it helps them.

It's a miracle drug for reducing immune overreach, like better than anything we know of. This is also completely outside of the weight loss effects. My lower back is improved by it.

It'll come to be known that these drugs are far better for people in a broad way than even thought today. They seem to have at least 4 effects that individually should be considered a "miracle."

I know you're getting a lot of "this worked for me" responses and I wanted to throw one more in. I used to have lower back problems all the time, but after following a strength training program for the olympic lifts with a personal trainer, generally the only time I have lower back pain now is if I've gone too hard to deadlifts or rows, not from general day to day things.
SW033291 or MF-300 might be interesting to look out for with spinal function. https://www.sciencedaily.com/releases/2026/01/260120000333.h...
I have a bad disc, and while its still bad, a couple weeks of freestyle swimming workouts makes it not hurt for a year or two and lets me mountain bike comfortably again. Something to try if the usual stuff doesn't work, as it tends not to!

This was the disc between lumbar and sacrum. 1,000 ways to have a bad disc so results will vary a lot!

Funny, after semaglutide I developed moderate arthritis in my MTP(foot) joint.

I wonder if it was gout because it seemed to come on fast. They say semaglutide shouldn't cause gout but I'm not convinced. It has some very weird effects on my hydration. I drink a fair amount of water, but specifically at night I now have to urinate a dozen times throughout the night and wake up with my mouth almost dried shut.

I've lost 10% of my bodyweight(probably >1/3 muscle, sadly) which is great and it's taking the load off my joints, but man this foot thing is a bummer. I need to find a sports Dr because most foot docs seem to take the "just stop running/hiking and switch to biking/swimming" approach which doesn't work for me.

That kind of damage takes many years. Do you have scans from prior years? I also discovered I have arthritis in the ankle recently and there were no pain symptoms, only joint instability and issues higher up on the leg. This was probably caused by either genetics or ankle trauma from childhood that eventually reared its head in my 30s.
If it is gout you should try eating cherries I have seen them be incredibly helpful.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6914931/

https://www.sciencedirect.com/science/article/abs/pii/S22124...

GLP-1 and GIP are both hormones the human body makes in the gut. The famous drugs are mimicking those hormones. This is more akin to taking supplemental testosterone than it is to taking Fen-Phen or whatever.
Currently there is a torrent of research on the benefits of GLP1s. This raises doubts as most are not backed by solid hypothesis. The same happened almost a century earlier when aspirin was explored as super drug. A key metric is the NNT (number needed to treat), ie how many people should take the drug for one to meet the primary goal.
Most of the results here are in mice, but they apparently did a small pilot study in humans:

https://www.chictr.org.cn/showprojEN.html?proj=176336

To the extent that there are results, they're paywalled. But, oddly, the entire article appears to be posted in the supplemental information section:

https://www.cell.com/cms/10.1016/j.cmet.2026.01.008/attachme...

From Figure 1, the effect size in mice was fairly large.

Pages 9 and 10 give a very brief description of the human trial. It looks like they did not make any effort to disentangle effects due to weight loss from effects independent of weight loss in humans. The humans in the study group had a 17% increase in knee cartilage thickness, and the dose used was (see page e3):

"Participants receiving SG treatment initiated with a dose of 0.25 mg in the first week, and increased the dose in a stepwise manner each subsequent week until reaching the target dose of 0.5 mg/week (incremental steps of 0.125 mg)."

AIUI this matches the current recommended starting dosage for diabetes and is considerably lower than the dosages used for weight loss.

There are other clinical trials, such as one for Orforglipron, which are also studying this specifically.
I have to chime in here. The full text is paywalled but if you have a subscription or institutional access the devil is in the details.

The "pilot study" the authors performed was an n=20 with 30% dropout, meaning 14 finished the study, 6/10 in the non-semaglutide arm and 8/10 in the semaglutide arm. They did not include participants who dropped out in their final analyses which is a big methodological flaw. I could go on about their choice in and measurement of outcomes, but suffice to say with only 14 participants these results should be taken with a grain of salt.

Further, they did extensive molecular biological studies in mice. There have been MANY (dozens) of murine (mouse) studies showing beneficial effects of various compounds / interventions on mouse knee osteoarthritis. None of them have translated into a therapy for the human disease. Mice live 2-3 years and have very different knee biomechanics than humans.

Appreciate the authors investigative efforts, but more confirmatory studies are needed before I'll be injecting semaglutide into my knee.

I wonder if the real problem is that we are really sick, and we just don't realize it: weight and eating too much processed food, so anything that improve these 2 aspects has also a lot of uncorrelated benefits.
We don’t see lots of stories about how dieting causes cartilage to grow back.
I'm always wary of such claims as it is not unusual for companies to extend the use of their drugs, after all the patent expires in some years
I have a friend who was put on a GLP-1 and had an astonishing reduction in arthritis pain.
Typo in the title - “independant”
I hope this goes through clinical trials before my joints degrade completely
is Big Pharma going to invest in any of the other peptides or is it just one and done?

because the underground grey market seems to be snowballing for all kinds of diseases and symptoms

just very dangerous without any regulation

Title is misspelled, should be “independent”.
did anyone actually read the article to figure out if these results are at all reliable?
Why are studies on mice so popular on HN?
Ok it makes sense now. This is fasting.
I'll probably be downvoted for this but honestly it seems like a lot of the benefits of semiglutide are literally just benefits of fasting.
the new ivermectin...