[HN Gopher] Semaglutide improves knee osteoarthritis independant...
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Semaglutide improves knee osteoarthritis independant of weight loss
Author : randycupertino
Score : 166 points
Date : 2026-02-10 16:55 UTC (6 hours ago)
(HTM) web link (www.cell.com)
(TXT) w3m dump (www.cell.com)
| randycupertino wrote:
| 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 wrote:
| 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 wrote:
| > 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 wrote:
| > 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 wrote:
| > 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.
| gib444 wrote:
| 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 wrote:
| 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 wrote:
| Nice. I added quite a lot of powder magnesium to my
| morning shake, did nothing.
| johnmaguire wrote:
| 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.
| Dma54rhs wrote:
| 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.
| Fogest wrote:
| Ultimately you get these extreme issues if you ignore a
| problem for too long. If you are becoming constipated and
| let it continue for many days on end without seeking some
| kind of treatment I feel that you are kinda to blame. I had
| some constipations at one point while on it and used some
| over the counter style fiber products and stool softeners
| to deal with the problem. If I ignored the problem of
| course I could potentially end up in these more extreme
| situations.
|
| I think if people are choosing to use such medications they
| should make sure they are aware of the potential
| complications and are vigilant with their health to ensure
| these extreme side effects are avoided.
| gib444 wrote:
| Fibre and stool softeners did nothing for me. Nor
| increasing water. Nor exercise. Nor massaging my stomach.
| Nor senna
|
| Only a magnesium drink ("Milk of Magnesia") or bisocodyl,
| neither of which are pleasant to take regularly as they
| result only in diarrhoea
|
| It's hard to balance trying to let your body do its thing
| with less extreme method and resorting to the nuclear
| option. You also have to write off a day and not go
| anywhere after taking those
|
| It's very much related to the drug and not just
| "ignoring" something
| rootusrootus wrote:
| Try miralax yet? It's basically tasteless in a glass of
| water.
| Fogest wrote:
| I only had an issue because I was taking an iron
| supplement at the same time which also can further cause
| constipation. I stopped taking that and it resolved my
| constipation issues.
|
| I'm not too sure what you're referring to with a "write
| off day". I am on the highest dose currently and don't
| have this issue. I maybe get some sleepiness the day
| after taking it but I can still do things. However that
| effect has also subsided a lot after taking it for long
| over.
|
| Every medication will have pros and cons. I'm having huge
| success on the medication and the slight issues I have
| are a worthy tradeoff personally.
| normie3000 wrote:
| > I'm not too sure what you're referring to with a "write
| off day".
|
| Some people aren't comfortable leaving the house when
| their rear is flowing like Niagara Falls.
| Fogest wrote:
| Oh wow that sounds like the opposite issue! I've only had
| the other problem where it's not coming out. It's funny
| how medications can cause issues where they constipate
| people, but then also have the opposite problem where
| they make people have diahrea.
| malfist wrote:
| For what it's worth, GLP-1s helped significantly with my
| IBS-D, and current research shows they're more effective
| and better tolerated than bile acid sequestrants.
|
| YMMV
| rootusrootus wrote:
| I'm totally with you. I've been lucky because a daily scoop
| of miralax has made me regular; unsolvable constipation
| would be absolutely miserable.
| r00fus wrote:
| If you don't have a regime that supports the medication,
| you could suffer some real problems. Drinking a LOT of
| water is mandatory. As well as eating lots of fiber - like
| good p-fruits (plum/pear/peach/etc) or benefiber/laxative.
|
| I've had no problems following the advice of my weight loss
| program and r/Zepbound etc.
| normie3000 wrote:
| Pineapple?
| stavros wrote:
| 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 wrote:
| Have you considered tirzepatide (ie, Zepbound/Mounjaro)? I
| know several people who responded poorly to Wegovy who did
| great on Zep.
| stavros wrote:
| Yes, neither works for me. I managed to tolerate
| tirzepatide better (once), but it barely works at that
| point.
| RobotToaster wrote:
| I keep expecting for them to discover some horrible side
| effect. I wonder if people thought the same when they
| discovered antibiotics though.
| foxyv wrote:
| 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.
| JumpCrisscross wrote:
| 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 wrote:
| 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.
| nradov wrote:
| GLP-1 drugs carry a small risk of gastroparesis, which can
| be severe in some patients. I wouldn't recommend avoiding
| using them due to that risk if medically indicated but
| patients should be aware.
|
| https://www.centraloregondaily.com/news/consumer/glp-1-weig
| h...
| amanaplanacanal wrote:
| Diabetes can cause gastroparesis too. I assume a large
| number of folks taking these drugs are diabetic.
| alexjplant wrote:
| Stomach paralysis is apparently a known side effect [1].
| There are also lots of anecdotes about lesser (but still
| foul) digestive surprises that are too unpleasant for me to
| bother elaborating on here.
|
| I was on my thiccboi swag for the latter half of last year
| and am presently working it off by rebuilding my fitness
| base with kettlebells and cardio. I'd rather do this than
| GLP-1s not because I'm some sort of iron-willed badass so
| much as I'm simply distrustful of anything that messes with
| one's metabolism so severely. While these drugs are useful
| for the morbidly obese and diabetics I simply can't imagine
| how or why anybody would go on them for aesthetic or off-
| label purposes.
|
| [1] https://www.webmd.com/obesity/ozempic-and-stomach-
| paralysis
| supern0va wrote:
| >Stomach paralysis is apparently a known side effect [1].
| There are also lots of anecdotes about lesser (but still
| foul) digestive surprises that are too unpleasant for me
| to bother elaborating on here.
|
| These are real, but they're also not permanent, and are
| why you start on a low dose to evaluate how your body
| reacts to the medication. My spouse is a long time GLP-1
| user (coming up on four years now) and had mild (or more)
| bouts of several of these digestive related systems.
|
| However, within six months these had greatly diminished.
| And by the one year mark, even at the highest dose, they
| were essentially gone and have remained a non-issue
| since.
|
| You should certainly be mindful of side effects, and
| follow the recommended dosage scale up, which should be
| monitored by your doctor.
|
| >I was on my thiccboi swag for the latter half of last
| year and am presently working it off by rebuilding my
| fitness base with kettlebells and cardio. I'd rather do
| this than GLP-1s not because I'm some sort of iron-willed
| badass so much as I'm simply distrustful of anything that
| messes with one's metabolism so severely. While these
| drugs are useful for the morbidly obese and diabetics I
| simply can't imagine how or why anybody would go on them
| for aesthetic or off-label purposes.
|
| I do think folks with obesity fall into one of two camps
| (or somewhere on a spectrum between): those that are in
| that place because they don't put in any effort, eat
| whatever they want, don't workout, and so on.
|
| And then there are folks like my spouse. They were able
| to lose weight in the past, but only through continued
| suffering. To be "just" overweight, they needed to be
| working out constantly and in a state of _always_ feeling
| hungry. They never reached an equilibrium where it wasn
| 't agony to maintain that weight, and after months/years
| would always rebound.
|
| For them, a GLP-1 was the only thing that ever quieted
| the food noise. They workout constantly still and are in
| the best shape of their life. It wasn't entirely the
| GLP-1, but that gave them the tool to quiet the noise and
| get to a state where fitness could be fun/sustainable,
| and now they're killing it.
|
| So, the TL;DR is that some people need this tool, and
| it's not necessarily an either/or. It can be one part in
| a series of positive changes that lead to better health
| and well-being.
| autoexec wrote:
| > 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 wrote:
| > 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 wrote:
| 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 wrote:
| 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 wrote:
| 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?
| autoexec wrote:
| It's not so much a massive conspiracy as it is the known
| reality of how these companies operate. There is very
| little risk as oversight and real accountability are
| basically non-existent
|
| Novo Nordisk has even demonstrated their willingness to
| ignore disclosure requirements
| (https://www.pslhub.org/blogs/entry/7950-wegovy-maker-
| novo-no...) multiple times even
| (https://news.sky.com/story/ozempic-maker-novo-nordisk-
| failed...) but the problem is everywhere including
| research
|
| Here are just some examples:
|
| > Cross-sectional studies across a heterogeneous set of
| conditions suggest that between 29 and 69 % of published
| clinical trial reports include disclosures of conflicts
| of interest. Studies measuring undisclosed conflicts of
| interest suggest that between 43 and 69 % of study
| reports and other articles fail to include disclosures of
| conflicts of interest
| (https://pmc.ncbi.nlm.nih.gov/articles/PMC4854425/)
|
| > chief medical officer at Memorial Sloan Kettering
| Cancer Center in New York, failed to disclose relevant
| industry ties in dozens of research articles since 2013.
| (https://ashpublications.org/ashclinicalnews/news/4092/Le
| adin...)
|
| > one in four Australian authors in 120 trials had at
| least one undeclared conflict, with an average value of
| undisclosed payment at almost AU $9000.
| (https://www.sydney.edu.au/news-
| opinion/news/2022/03/14/many-...)
| lysace wrote:
| I noticed that just in the past two hours you have
| provided detailed skepticism/commentary in these topics:
|
| - Semaglutide
|
| - App addiction for kids
|
| - Fake news via tiktok
|
| I guess what I'm asking is: are you really going deep, or
| just blasting us with links?
| autoexec wrote:
| I only provided examples in case there was any doubt that
| failure to disclose ties to the pharmaceutical industry
| was a known and large scale problem after the suggestion
| that it was some kind of conspiracy theory. Skepticism in
| the case of these drug companies is warranted.
|
| As for the variety of the things I've commented on, I can
| only blame procrastination and the contents of the front
| page. I got a lot more work done monday afternoon, I
| promise.
| throaway1998 wrote:
| There's no case to be made for calling these drugs snake
| oil. They're well-proven to have a host of benefits
| beyond their specified use. Their promotion by the makers
| of the drug doesn't change that.
| sReinwald wrote:
| 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 wrote:
| That would go in line with what I've read of it helping
| people with mild addictions.
| deinonychus wrote:
| 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 wrote:
| 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 is a good starting point.
| cthalupa wrote:
| I'll note that calling it the gray market really is
| people uncomfortable with the idea of buying drugs from a
| drug dealer trying to find a way to make this more
| palatable.
|
| That's not a judgment thing on my part - I've got a
| freezer full of Chinese peptides, among other things.
|
| But the raw API on all of this stuff is coming from China
| in a way that is effectively unregulated and with no
| recourse if anything goes wrong. Underground Chinese labs
| get raided and shut down (usually because they're also
| involved in producing AAS or opioid precursors) often
| leaving millions of dollars in unfulfilled product.
| People get peptides with 0 active ingredient. People get
| peptides contaminated with disinfectant and have adverse
| reactions. People get mislabeled peptides. People get
| radically underdosed or overdoses peptides. And when a
| controversy hits, these labs close up shop one day and
| come back a week later under a new name. If you get a
| vial full of something truly harmful to you and you die,
| your loved ones have zero recourse.
|
| Your local weed dealer has infinitely more accountability
| than these labs.
|
| Testing isn't a panacea - people do endotoxin, heavy
| metal, HPLC, etc., but GCMS and similar basically never
| happens - and without knowing what the potential
| substances are the automatching to peaks even for GCMS is
| often inaccurate to the point of uselessness."Purity"
| reports on HPLC don't measure everything in the vial -
| just how pure the targeted peak is. It'll catch protein
| depredations, but it wouldn't tell you if there was a
| bunch of anthrax in the vial.
|
| For me, the calculus still makes sense. I've got access
| to things that have worked incredibly well for me that
| are not yet available in the US, or in some cases, not
| likely to ever be. But the "gray" market is buying from
| overseas drug dealers that don't particularly give a fuck
| about you. They don't want to hurt you - you spend less
| money if they do - but they also aren't going out of
| their way to look after you. Most of them only started
| HPLC tests because the bodybuilding community demanded
| it, and these guys were selling AAS and HGH to them
| before they got into the GLP-1s, and then it became the
| standard.
|
| These aren't parallel import goods getting sold in areas
| where they aren't supposed to or unauthorized retailers.
| These are drug dealers that get shut down by the Chinese
| government on a regular basis. Go look up QSC, SSA, SRY -
| and those are just some of the biggest names from the
| past year or so.
| papascrubs wrote:
| I like to call it the "gray" market because the
| substances themselves are gray, not because of their
| source. My weed dealer doesn't sell GLPs (yet, but I can
| see that coming). I haven't seen anyone arrested for
| having GLPs yet either-- although I have seen plenty of
| US based vendors have to close up shop due to legal
| pressure.
|
| I do that believe that risk can be (mostly) mitigated,
| mainly by sticking with longstanding vendors and by
| trying to minimize risk with the actual substances
| (researching proper dosing protocol, batch testing, not
| assuming dosing, starting out on lower dosing with new
| kits etc). There is definitely risk associated, that said
| I'm often dabbling in non-FDA approved substances, so
| regardless I have zero recourse if something happens.
|
| Are there any testing/safety protocols that you follow?
| sigilis wrote:
| If it helps, I don't think that there is anything to be
| ashamed of to want to try new things even if you recognize
| it is inadvisable. If there were no physical consequences,
| I'd like to try all sorts of medicines to see what effect
| they would have on me.
|
| As a user of Mounjaro, obtained from a doctor, I find the
| experience very interesting. It has all sorts of weird side
| effects that I don't expect. As a bioinformatician in
| training it's great fun to speculate about the causes,
| pathways, signals, and whatnot that might be involved as
| this drug perturbs so much stuff in my system.
|
| It's not pleasurable per se, but it is interesting. I have
| changed my food habits significantly without actually
| trying. I think I was too impatient to eat to cook if that
| makes sense. Weirdly, foods taste better to me which I did
| not expect. I also have found myself really enjoying my
| hobbies more. This has resulted in a lot of 3d printer
| filament purchases, so my impulse control may not have been
| helped much.
|
| As far as experimenting on yourself, it will likely require
| the cumulative effect of weeks or months to notice changes
| in non-food habits if such changes occur at all.
|
| There's probably some online doctor that will prescribe
| this thing to you for several hundred dollars/euros or
| whatever. You may suffer greatly for your curiosity,
| though. There are instances of very unpleasant side
| effects, some of which I experience personally.
| sReinwald wrote:
| It would probably be interesting, but if you are not
| overweight, the appetite suppression will likely make this
| not a very healthy or very fun experiment. I started at 5mg
| in October, and even on that smaller dose I had to force
| myself to eat even just ~800kcal a day - especially in the
| early weeks. When you have a lot of weight to lose, that's
| a pretty welcome effect. When you are already at a healthy
| weight, not so much. That caloric intake would put most
| adults into a pretty deep caloric deficit.
|
| I'd suspect if the effects on non-weight indications check
| out in studies, we might see drugs that could specifically
| target those effects without also slowing down your
| digestive tract. Addictions like nicotine and alcoholism
| and their consequences cost health insurance companies (and
| us as a society) billions of Euros/Dollars each year, so
| there'd be a strong incentive to pursue this.
| LeifCarrotson wrote:
| Are the drugs actually expensive, or just expensive for now
| because they can be?
|
| Modern society basically decided that adding flouride to
| drinking water and iodine to table salt for everyone was
| better than dealing with tooth decay and gout.
|
| I understand that peptide synthesis and cold-chain logistics
| are not as trivial as these elements, but this paper [1]
| estimates that GLP1 manufacturing costs can be under a dollar
| per person per month, orders of magnitude less than current
| market rates!
|
| Perhaps our future society will normalize taking a daily
| GLP-1 agonist with their other multivitamins at breakfast.
|
| [1]: https://jamanetwork.com/journals/jamanetworkopen/fullart
| icle...
| MattGaiser wrote:
| They are cheap now if you dig deep enough. Lots of vendors
| selling peptides.
| thisisit wrote:
| Can you give some examples? And are those reliable?
| dinkelberg wrote:
| Not an example, but maybe this is interesting for folks
| who haven't really heard of the peptide business before.
| https://www.theguardian.com/wellness/2026/feb/05/injectab
| le-...
| sReinwald wrote:
| I suspect a big reason for why Mounjaro is still fairly
| expensive here in Germany (I pay nearly EUR400 for a 10mg
| Qwickpen - a 12.5mg Qwickpen is nearly EUR500) is due to
| health insurance not being allowed to cover them for
| anything but diabetes treatment.
|
| If health insurance companies would be able to cover these
| drugs, there'd have to be negotiations between Eli Lilly
| and the insurance companies, and insurance companies have a
| bigger lever than individual patients who pay out of
| pocket. Self-payers are just price-takers. We pay whatever
| Eli Lilly wants us to pay.
| 01100011 wrote:
| On Wegovy(semaglutide) I haven't noticed any change in my
| binges or impulsiveness. Slightly worse(not dramatic)
| depressive episodes but that's about it.
| zemvpferreira wrote:
| I've been on Mounjaro and find it pretty inexpensive, but I'm
| using a high-dose pen for a low-dose injection. One 15mg pen
| is going to last me around 6 months at my current rate, so
| around 15 euros per week.
| CoastalCoder wrote:
| If it can somehow restore spinal disc function, I'm gonna start
| snorting the stuff.
| nwienert wrote:
| 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 wrote:
| Can you give some examples of immune overreach that are
| improved?
| wincy wrote:
| 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.
| JMKH42 wrote:
| 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!
| schnebbau wrote:
| 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.
| properbrew wrote:
| Do you have any links for how you did these stretches? I know
| someone that could do with trying this.
| schnebbau wrote:
| For hamstring stretch I find using a back extension station
| works well, doing one leg at a time (https://m.media-
| amazon.com/images/I/61TQEGNUgQL._AC_UF894,10...). Let
| gravity pull your torso down, which will stretch your
| hamstring. If that's not possible, using the corner of a
| wall works too
| (https://i.ytimg.com/vi/2U4ChnuL3JM/maxresdefault.jpg)
|
| For the McKenzie stretch (https://images.squarespace-
| cdn.com/content/v1/5e556aadfe97d3...), instead of just
| holding the stretch, do reps between laying flat and then
| going into the stretch. At the end of your final rep (I
| would do 8), rotate side to side gently when arched.
|
| Dead hangs: hang from a bar for 30 seconds, completely
| relaxed. Then 1 minute of rest. Repeat 3 times. This
| decompresses your spine.
| mrmuagi wrote:
| McKenzie stretched helped me rehab a pulled muscle in my
| lower back (originally thought it was a disc).
|
| Deadlifts also helped strengthen lower back muscles. Tight
| hamstrings from sitting on the computer all the time also
| didn't help. I'll try dead hangs.
| schnebbau wrote:
| Deadlifts are how I got into that mess. There are two types
| of deadlifter: those who have ruined their back, and those
| who haven't yet ruined their back.
|
| Romanian deadlifts are much safer. Also hip thrusts and
| weighted back extensions are good enough unless you're a
| competitive power lifter.
| boelboel wrote:
| SW033291 or MF-300 might be interesting to look out for with
| spinal function.
| https://www.sciencedaily.com/releases/2026/01/260120000333.h...
| malfist wrote:
| 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.
| waffletower wrote:
| There are other clinical trials, such as one for Orforglipron,
| which are also studying this specifically.
| lvspiff wrote:
| 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 wrote:
| If you don't mind sharing, at what dose did you see positive
| impact on mood?
| autoexec wrote:
| > 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 wrote:
| 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 wrote:
| 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.
| skipkey wrote:
| It's not just you. I've known several people who lost their
| desire to drink beer specifically on these drugs. I didn't
| personally experience it, but then I am more of a whiskey
| guy.
| jaggederest wrote:
| The really beautiful thing now is that, with the evidence
| from GLP-1 drugs as a class, we're seeing 3 things: new
| targets for all kinds of things, that were previously
| discarded as "too difficult to make into medication", and in
| addition, injectable treatments - for a long, long time
| anything that required injections was just ruled out at the
| mechanism level. The third thing is that pharmaceutical
| industry has learned how to hit multiple targets with a
| single drug - previously most drugs were formulated to hit at
| most one or two receptors, and now we're seeing work on quad
| or 5-way drugs.
|
| I'm super optimistic, the pipeline for future medications in
| these classes and other related ones are enormous. Huge
| effects both for me personally but for the world as a whole,
| a world in which obesity and other chronic behavioral
| conditions are treated more like cancer than smoking - even
| smoking itself!
| samuelson wrote:
| I've had a similar experience where I'd be craving a beer,
| but not really craving alcohol since wine or spirits didn't
| sound appealing at all. I think it might actually be the hops
| and not the alcohol.
|
| I don't know if it's common in the UK, but in the US, a lot
| of breweries have started making hop water. I've found that
| it can really scratch that itch. Even just a hop tea might
| work if you can't find pre-made hop water.
|
| It sounds weird, but it's actually delicious with nice floral
| and citrus notes and just enough bitterness that you don't
| drink it too quickly.
| ck2 wrote:
| 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 wrote:
| It seems like pharma developed many of them, but it takes a
| while to get them to market.
| renewiltord wrote:
| 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 wrote:
| Typo in the title - "independant"
| renewiltord wrote:
| One thing we have to remember is that we don't know the long term
| effects of these things. Just like we don't know the long term
| effects of the MMR 2. The first infants vaccinated with that are
| only in their fifties or early sixties. For all we know, the
| measles vaccine insta-kills people at 70.
|
| We don't know anything. We are complete ignorant floating through
| the void. If I drop a rock and it falls I cannot tell if the next
| rock I drop will fall. We can't know. We are unknowing. Anything
| could happen.
| malfist wrote:
| I can't tell if this is a sarcastic response in bad taste, or
| if it's an authentic, if misguided, opinion.
| landryraccoon wrote:
| 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.
| rsyring wrote:
| 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.
| throwaway173738 wrote:
| 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 wrote:
| Okay I confess to getting taken by this comment. I downvoted
| and retracted. Sometimes sarcasm is too close to widely held
| beliefs.
| clhodapp wrote:
| Good point. Perhaps if you take them for 40 years, you become
| biologically immortal. Who can really say?
| engelo_b wrote:
| if this actually prevents expensive knee replacements, the ROI
| for insurers should be a no-brainer. the challenge is the high
| monthly cost vs long-term surgery savings it's hard to model when
| people switch carriers every few years and take the health
| benefit with them.
| mirthflat83 wrote:
| 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
| cultofmetatron wrote:
| 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 wrote:
| You think fasting improves knee osteoarthritis independent of
| weight loss?
| cultofmetatron wrote:
| 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.
| MPSimmons wrote:
| 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...
| MattGaiser wrote:
| Why is that unlikely?
|
| There are other known molecules that are many to many like
| cortisol, testosterone, and insulin.
| pertymcpert wrote:
| I mean...if you read the paper they control for that.
| estearum wrote:
| Hormones do a lot all over your body.
|
| You're commenting on a paper that specifically found OA
| improvement without weight loss improvement...
| RobotToaster wrote:
| There's GLP-1 receptors in the brain, they induce neurogenesis
| kixiQu wrote:
| 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.
| FeteCommuniste wrote:
| > 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.
| MPSimmons wrote:
| sorry, fixed!
| rustyhancock wrote:
| 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?
| ericmay wrote:
| > There's a synergy here, eat healthier, reduce blood sugar
| spikes, lose weight.
|
| I'm not a doctor, this isn't medical advice, I'm just
| bullshitting on the Internet. I know this is a controversial
| topic and the science doesn't appear to be settled.
|
| My understanding about how artificial sweeteners work in part
| is that they don't have a caloric impact but still cause an
| insulin response. I've avoided them as best as I can. Some
| people believe there's a free ride to be had with them -
| drink Diet Coke and nothing happens, but I'm not so sure
| that's the case.
|
| If a sugary drink causes an insulin response, and perhaps
| that response is different of course, but if it causes an
| insulin response, and so do "sugar-free" drinks - we seem to
| be in a world where a large number of people are still
| dealing with issues related to sugar that they maybe aren't
| expecting. I just have a hard time believe there's a free
| ride with "sugar-free" drinks. This response probably leads
| to more cravings for so-called empty calories. A lot of
| people I find viscously defend "sugar-free" drinks which
| leads me to suspect there's something there too.
|
| If you grow up with an awful diet, like I did, not centered
| around so-called whole foods and actual cooking I think you
| wind up in a vicious cycle of sugar, sugar substitutes, and
| other empty-calorie style foods that all feed the same
| biological addiction mechanism. You get fatter and fatter and
| no amount of exercise will work (you can't outrun a bad diet)
| and then add in our modern lifestyle and of course we're all
| pretty dang sick.
| david-gpu wrote:
| _> My understanding about how artificial sweeteners work in
| part is that they don 't have a caloric impact but still
| cause an insulin response._
|
| Some sweeteners appear to trigger insulin secretion, some
| don't.
|
| [0] https://www.dietdoctor.com/low-carb/sweeteners
|
| [1] https://www.diabetes.co.uk/in-depth/study-review-do-
| sweetene...
| rustyhancock wrote:
| Interestingly seeing, or smelling foods can cause insulin
| release[0]. Perhaps it's not surprising that tasting
| foods would.
|
| But it does make me wonder. If evolution was so concerned
| about blood sugar control it led to insulin release even
| before you ate (and that in evolutionary terms foods were
| very low in sugar and simple carbs). What must a doughnut
| do to our physiology?
|
| [0] https://www.sciencedirect.com/science/article/abs/pii
| /002604...
| ericmay wrote:
| > What must a doughnut do to our physiology?
|
| Maybe that's why my hair is falling out!
|
| Interesting article (to both of you actually). Thanks for
| sharing.
| jvandreae wrote:
| That article seems a bit misleading. While some
| _sweetener packets_ , such as equal and splenda contain
| some sugar, I don't believe this is necessarily true when
| they are used in other products. A quick google implies
| that, for example, Diet Coke (my beloved) does not
| contain any real sugar, only aspartame. So it seems
| disingenuous to compare the metabolic impact of a
| sugar/aspartame blend to pure aspartame.
| david-gpu wrote:
| The article goes into a lot more depth than that and
| contains links to the peer-reviewed research that it is
| summarizing.
| cthalupa wrote:
| If they're not losing weight they're not restricting calories.
| Energy has to come from somewhere.
|
| They explicitly controlled for all of this.
| lookdangerous wrote:
| Ok it makes sense now. This is fasting.
| dupdup wrote:
| yes and ramadan is coming lets do the fasting and get healthier
| :) it is a little bit long but we will see
| 01100011 wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| 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...
| framebit wrote:
| 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 wrote:
| 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 wrote:
| I hope this goes through clinical trials before my joints degrade
| completely
| joofbro wrote:
| did anyone actually read the article to figure out if these
| results are at all reliable?
| overtone1000 wrote:
| Why are studies on mice so popular on HN?
| vb-8448 wrote:
| 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 wrote:
| We don't see lots of stories about how dieting causes cartilage
| to grow back.
| gwern wrote:
| Fulltext:
| https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf
| amluto wrote:
| 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.
| tsoukase wrote:
| 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 wrote:
| 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 wrote:
| Title is misspelled, should be "independent".
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