7 ms·

Semaglutide improves knee osteoarthritis independant of weight loss

192 points by randycupertino 9mo ago

randycupertino 9mo ago
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.
- lysace 9mo ago
  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).
  - mhurron 9mo ago
    > Seems like a wonder drug to me Not really, it's that hormones don't do just one thing in the body. GLP-1 isn't just some weight management hormone. > The one that stuck with me from a few weeks ago went like 'I puked up my own poop.' That happens if you let constipation go on far too long, and is not something unique to GLP-1 meds.
    - nwienert 9mo ago
      > Not really This made me actually laugh. A drug that cures obesity and addiction alone would be a wonder drug. This one also improves about a hundred odd immune disorders, including being a better general allergy drug than just about anything. My own extremely rare and terribly painful immune disorder is basically entirely cured by it - it completely changed my life, making even sleeping far better. But not just me, I have friends who have lifelong terrible allergies gone, lifelong pack-a-day smoking addictions completely gone, and so on... "Not really" is truly either the most pessimistic take I've ever heard, or hopefully just completely misinformed.
      - mhurron 9mo ago
        > A drug that cures obesity and addiction alone would be a wonder drug. A drug that influences a hormone causing effects on everything that hormone is involved in shouldn't be considered a wonder drug, it should be expected functionality. It's only a wonder drug that does all these miraculous things if you think GLP-1 is only a weight management hormone. It's not, and you should expect effects anywhere it is involved in. A short list of tissues we know GLP-1 is involved in processes is: - heart - tongue - adipose tissue - muscles - bones - kidneys - liver - lungs Effects on these aren't miracles, they should be expected. I am happy to hear you saw so many improvements, but it's because you had an issue with a hormone that is involved in a lot of things in the body. So it was going to express a lot of problems. It's not surprising that you see a lot of improvements when you begin to manage the underlying cause.
        nwienert 9mo ago
        The fact you assume to know what my issue is is wild, and especially since you're just completely wrong - I have no direct GLP-1 issue, my levels are normal. It's clear you have no idea what you're talking about. Every single case I'm talking about outside weight loss has nothing to do with having a deficiency of that hormone, rather it's fixed by the hormone raising. And given it was impossible to do otherwise, it's a wonder drug, of course. You don't really define wonder by how simple it is, but by the effects, which are tremendously beneficial to many. Further, I stand by my prediction that in the long run the vast majority of why this drug will be considered an once-a-generation discovery, is not due to weight loss or appetite control, but in fact it's seeming broad spectrum benefits across many systems. And actually your list of effects it has are interesting, because if you investigate deeply the studies published, you'll find that the results are overwhelmingly positive - brain, heart, many organs.
  - gib444 9mo ago
    The constipation is REAL though. Like 10 plus days real. That scare story might be extreme but severe constipation is pretty common (and fecal vomiting can be a result of extreme constipation/impaction I believe)
    - lvspiff 9mo ago
      I've been taking the pill form of magnesium citrate and it helped SOO much im back to every day to every other day
      - gib444 9mo ago
        Nice. I added quite a lot of powder magnesium to my morning shake, did nothing.
        deleted 9mo ago
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        radlad 9mo ago
        You mentioned elsewhere that milk of magnesia worked, so is it possible that you received a bunk product? I know this is a common issue with supplements and there are some neutral third-party test labs for this.
        gib444 9mo ago
        Possibly but it was from a family run company in Wales with a good reputation
      - Dma54rhs 9mo ago
        Some forms of magnesium trigger more stool my movement than others. And there are many forms. I had opposite problem with it, tried ti find what won't cause it since I have a problem with it too behind with. Also sour kraut triggers me almost always and instant toilet break.
    - deleted 9mo ago
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  - RobotToaster 9mo ago
    I keep expecting for them to discover some horrible side effect. I wonder if people thought the same when they discovered antibiotics though.
    - foxyv 9mo ago
      To be fair, we have seen some long term effects from antibiotic use. Especially with regards to gut biomes. However, the long term effect of not using them is oftentimes death or permanent disability. Don't see nearly as many amputations from infected scratches these days thankfully.
    - deleted 9mo ago
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    - JumpCrisscross 9mo ago
      Or like Vitamin C. There aren’t side effects to fixing a vitamin deficiency. This increasingly, to me, looks like that. (There are absolutely bad effects from overdoing it.)
      - ViktorRay 9mo ago
        Hey just want to add something. Vitamin C is a water soluble vitamin. It’s pretty damn hard to get Vitamin C toxicity from overconsumption. It’s not really something to worry about. This is true for all the water soluble vitamins. This isn’t true for the fat soluble vitamins. Those are Vitamin A, Vitamin E, Vitamin K and Vitamin D. You can overdose and get toxicity if you consume too much of these. For Vitamin D you can’t overdose from what your body generates from the skin but you can from the oral forms.
        RobotToaster 9mo ago
        My understanding is it's virtually impossible to overdose vitamin K (without injecting it anyway), and pretty difficult to do so with Vitamin D.
    - nradov 9mo ago
  - stavros 9mo ago
    For me, it really is a wonder drug. My blood test results were stellar when the drug worked for me. Unfortunately, with me, it either works and I get side effects, or it doesn't work at all. I feel minimal effects (and almost no weight loss) even on a 10mg dose.
    - r00fus 9mo ago
      Have you considered tirzepatide (ie, Zepbound/Mounjaro)? I know several people who responded poorly to Wegovy who did great on Zep.
      - stavros 9mo ago
        Yes, neither works for me. I managed to tolerate tirzepatide better (once), but it barely works at that point.
  - autoexec 9mo ago
    > Seems like a wonder drug to me. The benefits just keep piling up. That's a massive red flag. It's a common sign of snake oil when something claims to be the cure for a ton of completely unrelated conditions. While I do think these drugs are actually effective at some things, I also wonder how much they're being overprescribed already. It seems like there's a massive push to try to get insurance to cover the drug for just about anything and everything. I've never seen a drug advertised as aggressively either. The drug is helping people and improving lives and that's a good thing, but I'm not sure how much of the attention on this drug is just a massive scheme by phrama companies to get sales and how careful doctors and patients are being.
    - MattGaiser 9mo ago
      > It's a common sign of snake oil when something claims to be the cure for a ton of completely unrelated conditions. Except this is coming from the opposite direction. The drug is being noticed to seemingly cure unrelated conditions. The vendor is not selling it as that.
      - meatmanek 9mo ago
        There's always the chance that the manufacturers are behind some of these stories -- funding studies to find new markets, astroturfing success stories, etc.
      - autoexec 9mo ago
        Although I can't say it's what happened in this case, I suspect that the drug companies have a hand in some of the research showing the unexpected benefits of their product. While they do have to be careful about what they claim the drug does in conventional advertising, studies suggesting various benefits for this drug get a lot of attention in the media.
        cthalupa 9mo ago
        These studies have conflict of interest, funding, etc. disclosures. If it was Lilly and Novo pushing these, they'd either show up in those disclosures or you're suggesting a massive conspiracy to undermine the medical regulatory system to sell more drugs that they already have struggled to meet demand for for extended periods of time. Why would they kill a golden goose that shows no signs of stopping it's egg laying?
- sReinwald 9mo ago
  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.
  - thinkingtoilet 9mo ago
    That would go in line with what I've read of it helping people with mild addictions.
  - deinonychus 9mo ago
    That’s really neat. I’m ashamed that I have this wish that I were overweight and had an excuse to try a GLP1 just to see how it would affect my impulse control with non-food habits. I guess there’s not much stopping me from buying some unregulated drugs from the internet and self-experimenting, but I haven’t heard experiences from people deliberately using them for anything but weight.
    - papascrubs 9mo ago
      Depending on your appetite for risk, there's always the gray market. It's also a lot cheaper depending on what your insurance covers. I think I picked up a year's supply of semaglutide for under $200. I've been on some form of GLP for the last 2 years and for me there have been several tangible benefits related to ADHD. https://gray.guide https://gray.guide is a good starting point.
      - cthalupa 9mo ago
CoastalCoder 9mo ago
If it can somehow restore spinal disc function, I'm gonna start snorting the stuff.
- nwienert 9mo ago
  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."
  - quantumwoke 9mo ago
    Can you give some examples of immune overreach that are improved?
    - wincy 9mo ago
      My wife has had an autoimmune disease that’s caused inflammation for years. Absolutely terrible back pain. She had to rent a motorized scooter when we went to Disney World, and could barely walk a few hundred feet before having to stop and rest for years. Last year she started Zepbound (tirzepatide) and the inflammation went away, we went to Disney World again and she walked happily all day. Absolutely life changing. She didn’t even lose much weight and this was at the lowest dose.
      - nwienert 9mo ago
        Tirzepatide specifically seems especially beneficial, likewise here. Years of slowly increasing symptoms since I was young, lifelong annoying issues, basically all gone on it. And also not overweight at all, I take below lowest dose and skip most weeks now that it's under control.
- JMKH42 9mo ago
  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!
waffletower 9mo ago
There are other clinical trials, such as one for Orforglipron, which are also studying this specifically.
lvspiff 9mo ago
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.
- rsyring 9mo ago
  If you don't mind sharing, at what dose did you see positive impact on mood?
  - lvspiff 9mo ago
    The most noticeable jump has been at 10mg but i started noticing it from the beginning of 2.5 to 5 to 7.5 over a 6 month period but something about 10 just hit different but only on my 2nd month of it now. Less anxiety about things i was hit by before and mood improved overall
- autoexec 9mo ago
  > 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.
- 01100011 9mo ago
  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.
- bluescrn 9mo ago
  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.
ck2 9mo ago
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
- MattGaiser 9mo ago
  It seems like pharma developed many of them, but it takes a while to get them to market.
- renewiltord 9mo ago
  Yes, this is a class of thing that is obviously being studied. Check out tesamorelin etc. but there is also a Phase 1 somewhere for BPC-157. The peptides themselves are being used for everything but realistically, considering the costs, you have to innovate a little. Here’s a little example with GLP-1: the core biology and mechanism were well understood. But use was like the grey market peptides you were talking about: a daily injection. Half life is super short because DPP4 chews through. So you need some innovation first to make it last so that you can bring it to market. Perhaps they misread the market and didn’t realize that for sufficient weight loss people would inject daily. But anyway, the liraglutide, dulaglutide, semaglutide, are various attempts at this to preserve function while raising half life in the body. If you want to accelerate this research you’re really going to have to reform the whole process of medical testing and this and that but most things are not so dangerous that you need to rush to release a drug. Not everything is COVID-19 or obesity. Getting a PDA trial so some few people can heal faster from workout injuries is probably going to be a hard sell, even on this forum. I’m of the view that the combination of grey market and clean market supply is a great way to serve latent desire as well as safe mass access. One funny thing that a researcher told me (on seeing my lab notebook of my retatrutide self tests) is that it complicates baseline wide population studies. The total population is also losing weight, not just known GLP-1RA users. It turns out grandpa and grandma are reconstituting vials with BAC in New Salem, Oklahoma.
monkpit 9mo ago
Typo in the title - “independant”
renewiltord 9mo ago
[flagged]
- rsyring 9mo ago
  I think this is FUD. Haven't GLP-1s been around for 20+ year? The recent surge in popularity was due to new formulas that could be injected once per week instead of daily.
- malfist 9mo ago
  I can't tell if this is a sarcastic response in bad taste, or if it's an authentic, if misguided, opinion.
- landryraccoon 9mo ago
  Teenagers and people in their 20 don’t need these drugs anyway, and they’re the ones who should be most concerned about long term effects. But people in their 50s and older? What long term effect is going to show up before they die? At age 70 or 80 long term effects are basically completely irrelevant.
- throwaway173738 9mo ago
  I know you’re making fun of baseless skepticism here but I remember seeing at least three different “miracle weight loss drugs” hit the market, give people fantastic results, and then get pulled years after some terrible long term side effects. I also remember similar marketing around SSRIs like Paxil being miraculous and GPs prescribing them to teenagers, and that did not go well for teenage me. So forgive me if I’m a little skeptical here.
- rootusrootus 9mo ago
  Okay I confess to getting taken by this comment. I downvoted and retracted. Sometimes sarcasm is too close to widely held beliefs.
- deleted 9mo ago
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- clhodapp 9mo ago
engelo_b 9mo ago
[dead]
- mirthflat83 9mo ago
  In theory, yes, but until these medications become generic, it will continue to cause huge losses for insurance companies. The cost of these medicines alone is worth more than premiums
deleted 9mo ago
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cultofmetatron 9mo ago
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.
- DwnVoteHoneyPot 9mo ago
  You think fasting improves knee osteoarthritis independent of weight loss?
  - cultofmetatron 9mo ago
    fasting is generally highly correlative with weight loss. Its also correlative with reduction in inflammation which is often the underlying cause of arthritis in general. I also would be curious to see what the outcome of fasting would be in a person undertaking an 18 hour fast while consuming enough calories during the feeding window to maintain a caloric surplus.
- quacker 9mo ago
  It's a good idea. There are many studied benefits to (intermittent) fasting, for example: https://pmc.ncbi.nlm.nih.gov/articles/PMC11262566/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11262566/
MPSimmons 9mo ago
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/ https://pmc.ncbi.nlm.nih.gov/articles/PMC12431743/ [2] - https://med.stanford.edu/news/insights/2025/04/ozempic-addiction-glp-1s-mounjaro-lembke.html https://med.stanford.edu/news/insights/2025/04/ozempic-addic...
- MattGaiser 9mo ago
  Why is that unlikely? There are other known molecules that are many to many like cortisol, testosterone, and insulin.
- pertymcpert 9mo ago
  I mean...if you read the paper they control for that.
- estearum 9mo ago
  Hormones do a lot all over your body. You're commenting on a paper that specifically found OA improvement without weight loss improvement...
- RobotToaster 9mo ago
  There's GLP-1 receptors in the brain, they induce neurogenesis
- kixiQu 9mo ago
  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.
  - deleted 9mo ago
    [deleted]
lookdangerous 9mo ago
Ok it makes sense now. This is fasting.
- dupdup 9mo ago
  yes and ramadan is coming lets do the fasting and get healthier :) it is a little bit long but we will see
01100011 9mo ago
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.
- pertymcpert 9mo ago
  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.
  - 01100011 9mo ago
    My last x-ray in 11/2022 was perfect. Good joint spacing and no degenerative changes. That's over 3 years ago now though. One thing I think changed for me was that I switched to WFH full-time and wearing crocs all day. My arches subsequently collapsed. I have joint stiffness now as well, but the x-ray didn't show anything so I think it's perhaps sinus tarsi pain from the compression due to over-pronation.
- randycupertino 9mo ago
  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://pmc.ncbi.nlm.nih.gov/articles/PMC6914931/ https://www.sciencedirect.com/science/article/abs/pii/S2212429225014300 https://www.sciencedirect.com/science/article/abs/pii/S22124...
framebit 9mo ago
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.
wolfi1 9mo ago
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
cantalopes 9mo ago
I hope this goes through clinical trials before my joints degrade completely
deleted 9mo ago
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_usf6 9mo ago
did anyone actually read the article to figure out if these results are at all reliable?
overtone1000 9mo ago
Why are studies on mice so popular on HN?
- deleted 9mo ago
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vb-8448 9mo ago
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.
- NetMageSCW 9mo ago
  We don’t see lots of stories about how dieting causes cartilage to grow back.
  - vb-8448 9mo ago
    Very fee people are able to dieting for several months or even years, it requires strong mental commitment while with this new drugs the effort much lower.
    - lvspiff 9mo ago
      They are lifelong drugs though - you go off it and the weight and “food noise” come back. If you grow to used to them you have to switch from ozempic to moniourno to whatever diff thing then circle around again. Not saying the effort is the same just that its def not a decision to take lightly and just start doing thinking its a few shots and bam your down 50 lbs forever - still have to do the mental reprogramming to not eat the bad stuff and exercise regularly
gwern 9mo ago
Fulltext: https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf
amluto 9mo ago
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 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/attachment/f949ab6c-cd86-4189-b114-ae62328a246c/mmc4.pdf 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.
tsoukase 9mo ago
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.
spiewart 9mo ago
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.
DerekL 9mo ago
Title is misspelled, should be “independent”.
senectus1 9mo ago
the new ivermectin...
cleandreams 9mo ago
I have a friend who was put on a GLP-1 and had an astonishing reduction in arthritis pain.

192 points by randycupertino 9mo ago

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.

lysace 9mo ago
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).
- mhurron 9mo ago
  > Seems like a wonder drug to me Not really, it's that hormones don't do just one thing in the body. GLP-1 isn't just some weight management hormone. > The one that stuck with me from a few weeks ago went like 'I puked up my own poop.' That happens if you let constipation go on far too long, and is not something unique to GLP-1 meds.
  - nwienert 9mo ago
    > Not really This made me actually laugh. A drug that cures obesity and addiction alone would be a wonder drug. This one also improves about a hundred odd immune disorders, including being a better general allergy drug than just about anything. My own extremely rare and terribly painful immune disorder is basically entirely cured by it - it completely changed my life, making even sleeping far better. But not just me, I have friends who have lifelong terrible allergies gone, lifelong pack-a-day smoking addictions completely gone, and so on... "Not really" is truly either the most pessimistic take I've ever heard, or hopefully just completely misinformed.
    - mhurron 9mo ago
      > A drug that cures obesity and addiction alone would be a wonder drug. A drug that influences a hormone causing effects on everything that hormone is involved in shouldn't be considered a wonder drug, it should be expected functionality. It's only a wonder drug that does all these miraculous things if you think GLP-1 is only a weight management hormone. It's not, and you should expect effects anywhere it is involved in. A short list of tissues we know GLP-1 is involved in processes is: - heart - tongue - adipose tissue - muscles - bones - kidneys - liver - lungs Effects on these aren't miracles, they should be expected. I am happy to hear you saw so many improvements, but it's because you had an issue with a hormone that is involved in a lot of things in the body. So it was going to express a lot of problems. It's not surprising that you see a lot of improvements when you begin to manage the underlying cause.
      - nwienert 9mo ago
        The fact you assume to know what my issue is is wild, and especially since you're just completely wrong - I have no direct GLP-1 issue, my levels are normal. It's clear you have no idea what you're talking about. Every single case I'm talking about outside weight loss has nothing to do with having a deficiency of that hormone, rather it's fixed by the hormone raising. And given it was impossible to do otherwise, it's a wonder drug, of course. You don't really define wonder by how simple it is, but by the effects, which are tremendously beneficial to many. Further, I stand by my prediction that in the long run the vast majority of why this drug will be considered an once-a-generation discovery, is not due to weight loss or appetite control, but in fact it's seeming broad spectrum benefits across many systems. And actually your list of effects it has are interesting, because if you investigate deeply the studies published, you'll find that the results are overwhelmingly positive - brain, heart, many organs.
- gib444 9mo ago
  The constipation is REAL though. Like 10 plus days real. That scare story might be extreme but severe constipation is pretty common (and fecal vomiting can be a result of extreme constipation/impaction I believe)
  - lvspiff 9mo ago
    I've been taking the pill form of magnesium citrate and it helped SOO much im back to every day to every other day
    - gib444 9mo ago
      Nice. I added quite a lot of powder magnesium to my morning shake, did nothing.
      - deleted 9mo ago
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      - radlad 9mo ago
        You mentioned elsewhere that milk of magnesia worked, so is it possible that you received a bunk product? I know this is a common issue with supplements and there are some neutral third-party test labs for this.
        gib444 9mo ago
        Possibly but it was from a family run company in Wales with a good reputation
    - Dma54rhs 9mo ago
      Some forms of magnesium trigger more stool my movement than others. And there are many forms. I had opposite problem with it, tried ti find what won't cause it since I have a problem with it too behind with. Also sour kraut triggers me almost always and instant toilet break.
  - deleted 9mo ago
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- RobotToaster 9mo ago
  I keep expecting for them to discover some horrible side effect. I wonder if people thought the same when they discovered antibiotics though.
  - foxyv 9mo ago
    To be fair, we have seen some long term effects from antibiotic use. Especially with regards to gut biomes. However, the long term effect of not using them is oftentimes death or permanent disability. Don't see nearly as many amputations from infected scratches these days thankfully.
  - deleted 9mo ago
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  - JumpCrisscross 9mo ago
    Or like Vitamin C. There aren’t side effects to fixing a vitamin deficiency. This increasingly, to me, looks like that. (There are absolutely bad effects from overdoing it.)
    - ViktorRay 9mo ago
      Hey just want to add something. Vitamin C is a water soluble vitamin. It’s pretty damn hard to get Vitamin C toxicity from overconsumption. It’s not really something to worry about. This is true for all the water soluble vitamins. This isn’t true for the fat soluble vitamins. Those are Vitamin A, Vitamin E, Vitamin K and Vitamin D. You can overdose and get toxicity if you consume too much of these. For Vitamin D you can’t overdose from what your body generates from the skin but you can from the oral forms.
      - RobotToaster 9mo ago
        My understanding is it's virtually impossible to overdose vitamin K (without injecting it anyway), and pretty difficult to do so with Vitamin D.
  - nradov 9mo ago
- stavros 9mo ago
  For me, it really is a wonder drug. My blood test results were stellar when the drug worked for me. Unfortunately, with me, it either works and I get side effects, or it doesn't work at all. I feel minimal effects (and almost no weight loss) even on a 10mg dose.
  - r00fus 9mo ago
    Have you considered tirzepatide (ie, Zepbound/Mounjaro)? I know several people who responded poorly to Wegovy who did great on Zep.
    - stavros 9mo ago
      Yes, neither works for me. I managed to tolerate tirzepatide better (once), but it barely works at that point.
- autoexec 9mo ago
  > Seems like a wonder drug to me. The benefits just keep piling up. That's a massive red flag. It's a common sign of snake oil when something claims to be the cure for a ton of completely unrelated conditions. While I do think these drugs are actually effective at some things, I also wonder how much they're being overprescribed already. It seems like there's a massive push to try to get insurance to cover the drug for just about anything and everything. I've never seen a drug advertised as aggressively either. The drug is helping people and improving lives and that's a good thing, but I'm not sure how much of the attention on this drug is just a massive scheme by phrama companies to get sales and how careful doctors and patients are being.
  - MattGaiser 9mo ago
    > It's a common sign of snake oil when something claims to be the cure for a ton of completely unrelated conditions. Except this is coming from the opposite direction. The drug is being noticed to seemingly cure unrelated conditions. The vendor is not selling it as that.
    - meatmanek 9mo ago
      There's always the chance that the manufacturers are behind some of these stories -- funding studies to find new markets, astroturfing success stories, etc.
    - autoexec 9mo ago
      Although I can't say it's what happened in this case, I suspect that the drug companies have a hand in some of the research showing the unexpected benefits of their product. While they do have to be careful about what they claim the drug does in conventional advertising, studies suggesting various benefits for this drug get a lot of attention in the media.
      - cthalupa 9mo ago
        These studies have conflict of interest, funding, etc. disclosures. If it was Lilly and Novo pushing these, they'd either show up in those disclosures or you're suggesting a massive conspiracy to undermine the medical regulatory system to sell more drugs that they already have struggled to meet demand for for extended periods of time. Why would they kill a golden goose that shows no signs of stopping it's egg laying?
sReinwald 9mo ago
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.
- thinkingtoilet 9mo ago
  That would go in line with what I've read of it helping people with mild addictions.
- deinonychus 9mo ago
  That’s really neat. I’m ashamed that I have this wish that I were overweight and had an excuse to try a GLP1 just to see how it would affect my impulse control with non-food habits. I guess there’s not much stopping me from buying some unregulated drugs from the internet and self-experimenting, but I haven’t heard experiences from people deliberately using them for anything but weight.
  - papascrubs 9mo ago
    Depending on your appetite for risk, there's always the gray market. It's also a lot cheaper depending on what your insurance covers. I think I picked up a year's supply of semaglutide for under $200. I've been on some form of GLP for the last 2 years and for me there have been several tangible benefits related to ADHD. https://gray.guide https://gray.guide is a good starting point.
    - cthalupa 9mo ago

CoastalCoder 9mo ago

If it can somehow restore spinal disc function, I'm gonna start snorting the stuff.

nwienert 9mo ago
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."
- quantumwoke 9mo ago
  Can you give some examples of immune overreach that are improved?
  - wincy 9mo ago
    My wife has had an autoimmune disease that’s caused inflammation for years. Absolutely terrible back pain. She had to rent a motorized scooter when we went to Disney World, and could barely walk a few hundred feet before having to stop and rest for years. Last year she started Zepbound (tirzepatide) and the inflammation went away, we went to Disney World again and she walked happily all day. Absolutely life changing. She didn’t even lose much weight and this was at the lowest dose.
    - nwienert 9mo ago
      Tirzepatide specifically seems especially beneficial, likewise here. Years of slowly increasing symptoms since I was young, lifelong annoying issues, basically all gone on it. And also not overweight at all, I take below lowest dose and skip most weeks now that it's under control.
JMKH42 9mo ago
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!

waffletower 9mo ago

There are other clinical trials, such as one for Orforglipron, which are also studying this specifically.

lvspiff 9mo ago

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.

rsyring 9mo ago
If you don't mind sharing, at what dose did you see positive impact on mood?
- lvspiff 9mo ago
  The most noticeable jump has been at 10mg but i started noticing it from the beginning of 2.5 to 5 to 7.5 over a 6 month period but something about 10 just hit different but only on my 2nd month of it now. Less anxiety about things i was hit by before and mood improved overall
autoexec 9mo ago
> 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.
01100011 9mo ago
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.
bluescrn 9mo ago
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.

ck2 9mo ago

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

MattGaiser 9mo ago
It seems like pharma developed many of them, but it takes a while to get them to market.
renewiltord 9mo ago
Yes, this is a class of thing that is obviously being studied. Check out tesamorelin etc. but there is also a Phase 1 somewhere for BPC-157. The peptides themselves are being used for everything but realistically, considering the costs, you have to innovate a little. Here’s a little example with GLP-1: the core biology and mechanism were well understood. But use was like the grey market peptides you were talking about: a daily injection. Half life is super short because DPP4 chews through. So you need some innovation first to make it last so that you can bring it to market. Perhaps they misread the market and didn’t realize that for sufficient weight loss people would inject daily. But anyway, the liraglutide, dulaglutide, semaglutide, are various attempts at this to preserve function while raising half life in the body. If you want to accelerate this research you’re really going to have to reform the whole process of medical testing and this and that but most things are not so dangerous that you need to rush to release a drug. Not everything is COVID-19 or obesity. Getting a PDA trial so some few people can heal faster from workout injuries is probably going to be a hard sell, even on this forum. I’m of the view that the combination of grey market and clean market supply is a great way to serve latent desire as well as safe mass access. One funny thing that a researcher told me (on seeing my lab notebook of my retatrutide self tests) is that it complicates baseline wide population studies. The total population is also losing weight, not just known GLP-1RA users. It turns out grandpa and grandma are reconstituting vials with BAC in New Salem, Oklahoma.

monkpit 9mo ago

Typo in the title - “independant”

renewiltord 9mo ago

[flagged]

rsyring 9mo ago
I think this is FUD. Haven't GLP-1s been around for 20+ year? The recent surge in popularity was due to new formulas that could be injected once per week instead of daily.
malfist 9mo ago
I can't tell if this is a sarcastic response in bad taste, or if it's an authentic, if misguided, opinion.
landryraccoon 9mo ago
Teenagers and people in their 20 don’t need these drugs anyway, and they’re the ones who should be most concerned about long term effects. But people in their 50s and older? What long term effect is going to show up before they die? At age 70 or 80 long term effects are basically completely irrelevant.
throwaway173738 9mo ago
I know you’re making fun of baseless skepticism here but I remember seeing at least three different “miracle weight loss drugs” hit the market, give people fantastic results, and then get pulled years after some terrible long term side effects. I also remember similar marketing around SSRIs like Paxil being miraculous and GPs prescribing them to teenagers, and that did not go well for teenage me. So forgive me if I’m a little skeptical here.
rootusrootus 9mo ago
Okay I confess to getting taken by this comment. I downvoted and retracted. Sometimes sarcasm is too close to widely held beliefs.
deleted 9mo ago
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clhodapp 9mo ago

engelo_b 9mo ago

[dead]

mirthflat83 9mo ago
In theory, yes, but until these medications become generic, it will continue to cause huge losses for insurance companies. The cost of these medicines alone is worth more than premiums

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cultofmetatron 9mo ago

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.

DwnVoteHoneyPot 9mo ago
You think fasting improves knee osteoarthritis independent of weight loss?
- cultofmetatron 9mo ago
  fasting is generally highly correlative with weight loss. Its also correlative with reduction in inflammation which is often the underlying cause of arthritis in general. I also would be curious to see what the outcome of fasting would be in a person undertaking an 18 hour fast while consuming enough calories during the feeding window to maintain a caloric surplus.
quacker 9mo ago
It's a good idea. There are many studied benefits to (intermittent) fasting, for example: https://pmc.ncbi.nlm.nih.gov/articles/PMC11262566/ https://pmc.ncbi.nlm.nih.gov/articles/PMC11262566/

MPSimmons 9mo ago

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/ https://pmc.ncbi.nlm.nih.gov/articles/PMC12431743/ [2] - https://med.stanford.edu/news/insights/2025/04/ozempic-addiction-glp-1s-mounjaro-lembke.html https://med.stanford.edu/news/insights/2025/04/ozempic-addic...

MattGaiser 9mo ago
Why is that unlikely? There are other known molecules that are many to many like cortisol, testosterone, and insulin.
pertymcpert 9mo ago
I mean...if you read the paper they control for that.
estearum 9mo ago
Hormones do a lot all over your body. You're commenting on a paper that specifically found OA improvement without weight loss improvement...
RobotToaster 9mo ago
There's GLP-1 receptors in the brain, they induce neurogenesis
kixiQu 9mo ago
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.
- deleted 9mo ago
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lookdangerous 9mo ago

Ok it makes sense now. This is fasting.

dupdup 9mo ago
yes and ramadan is coming lets do the fasting and get healthier :) it is a little bit long but we will see

01100011 9mo ago

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.

pertymcpert 9mo ago
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.
- 01100011 9mo ago
  My last x-ray in 11/2022 was perfect. Good joint spacing and no degenerative changes. That's over 3 years ago now though. One thing I think changed for me was that I switched to WFH full-time and wearing crocs all day. My arches subsequently collapsed. I have joint stiffness now as well, but the x-ray didn't show anything so I think it's perhaps sinus tarsi pain from the compression due to over-pronation.
randycupertino 9mo ago
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://pmc.ncbi.nlm.nih.gov/articles/PMC6914931/ https://www.sciencedirect.com/science/article/abs/pii/S2212429225014300 https://www.sciencedirect.com/science/article/abs/pii/S22124...

framebit 9mo ago

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.

wolfi1 9mo ago

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

cantalopes 9mo ago

I hope this goes through clinical trials before my joints degrade completely

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_usf6 9mo ago

did anyone actually read the article to figure out if these results are at all reliable?

overtone1000 9mo ago

Why are studies on mice so popular on HN?

deleted 9mo ago
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vb-8448 9mo ago

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.

NetMageSCW 9mo ago
We don’t see lots of stories about how dieting causes cartilage to grow back.
- vb-8448 9mo ago
  Very fee people are able to dieting for several months or even years, it requires strong mental commitment while with this new drugs the effort much lower.
  - lvspiff 9mo ago
    They are lifelong drugs though - you go off it and the weight and “food noise” come back. If you grow to used to them you have to switch from ozempic to moniourno to whatever diff thing then circle around again. Not saying the effort is the same just that its def not a decision to take lightly and just start doing thinking its a few shots and bam your down 50 lbs forever - still have to do the mental reprogramming to not eat the bad stuff and exercise regularly

gwern 9mo ago

Fulltext: https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf

amluto 9mo ago

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 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/attachment/f949ab6c-cd86-4189-b114-ae62328a246c/mmc4.pdf 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.

tsoukase 9mo ago

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.

spiewart 9mo ago

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.

DerekL 9mo ago

Title is misspelled, should be “independent”.

senectus1 9mo ago

the new ivermectin...

cleandreams 9mo ago

I have a friend who was put on a GLP-1 and had an astonishing reduction in arthritis pain.