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by randycupertino·6mo ago·view on hn ↗
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.

2 comments
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.

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/fullarticle...

I suspect a big reason for why Mounjaro is still fairly expensive here in Germany (I pay nearly €400 for a 10mg Qwickpen - a 12.5mg Qwickpen is nearly €500) 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.

China can sell (at a profit) >99.8% pure tirzepatide, semaglutide, and retatrutide for <$3/weekly dose. This supply ends up at compounding pharmacies like Hims/Hers, but sometimes more directly to consumers through gray/black markets.

Another way to check if the marginal cost of production contributes to the cost of the drug is to compare the price of injectable semaglutide (~$1200) for around 10mg/month, to the price of oral semaglutide (Rybelsus), which is also (~$1,000) for around 420mg/month. That indicates that the cost of manufacturing semaglutide does not significantly contribute to the cost of the FDA-approved drug.

They are cheap now if you dig deep enough. Lots of vendors selling peptides.
Can you give some examples? And are those reliable?
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/injectable-...
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.
You are essentially amortizing a single dose over 6 months by micro-dosing and receiving a clearly sub-therapeutic dose. While that may work for your specific usage, it doesn't change the unit economics for someone who needs the standard therapeutic dose, which in my case at 10 mg is roughly €400 every 4 weeks.

It’s a bit like arguing that a Porsche GT3 RS is an 'affordable' car because the monthly payment is low, provided you finance it over 30 years. The sticker price hasn't changed, you've just engaged in extreme creative accounting to make it fit a monthly budget.

No, it's more like arguing a Miata will fit the same need as a GT3 at 1/20th the cost. Some people don't fit a Miata, but it's still a valid option for many. Though I am at a sub-clinical dose (not a microdose) I'm still losing between 1 and 3 pounds per week. Lots and lots of people optimise their dose and their pen size to make the economics and side effects more manageable. This is not at all unique to me. It's unfortunate if it doesn't fit your case but it is widely applicable nonetheless.
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.

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.

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.

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.

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.

That would go in line with what I've read of it helping people with mild addictions.
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.
I may well have done more hobby-related shopping 'binges'/impulse buying in place of eating/drinking binges while on Mounjaro.

But that wasn't such a bad thing - it was mostly due to feeling a bit more awake/alive in the evenings compared to when I'd be drinking or overeating.

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).

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)
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.

Pineapple?
I've been taking the pill form of magnesium citrate and it helped SOO much im back to every day to every other day
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.
Nice. I added quite a lot of powder magnesium to my morning shake, did nothing.
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

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.
>fecal vomiting

omg... new fear registered...

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.

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

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.
Have you considered tirzepatide (ie, Zepbound/Mounjaro)? I know several people who responded poorly to Wegovy who did great on Zep.
Yes, neither works for me. I managed to tolerate tirzepatide better (once), but it barely works at that point.
I keep expecting for them to discover some horrible side effect. I wonder if people thought the same when they discovered antibiotics though.
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

>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.

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-weigh...

Diabetes can cause gastroparesis too. I assume a large number of folks taking these drugs are diabetic.
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.
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.)
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.

> 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.

> 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.

There's always the chance that the manufacturers are behind some of these stories -- funding studies to find new markets, astroturfing success stories, etc.
"unrelated"

Are they, or is it just our incomplete understanding?

We still keep finding new and new surprising relationships in our bodies. Caries bacteria in colorectal cancer. Schizophrenia cured by bone marrow transplant. ALS cases induced by consumption of mushrooms (false morels).

I wouldn't be surprised if, say, reduction of systemic inflammation caused all sorts of unexpected effects body-wide.

> 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.

> 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.