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.
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?
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.
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?
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.
> 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.
You can't mention CICO in this forum, where people have a unique genetic disorder that makes them "extract more calories from the food" or "burn way less" than other people, barring them of any personal responsibility about what they put in their mouth.
Independent of weight loss, semaglutide (Ozempic) improves knee osteoarthritis by cartilage restoration, in both the mouse model and a small randomized clinical trial.
Old thinking was the benefit of GLP-1 drugs (like Ozempic) was solely from weight loss, however studies are showing there are other unique benefits. It's probably that semaglutide reduces inflammation allowing the body to repair and improves mitochondrial function in cartilage cells.
One thing I have noticed on Mounjaro is a (at least subjectively) significant decrease in impulse spending / buying random crap off Amazon. I have ADHD and that has been a real problem for quite a while - even with ADHD medication (Elvanse/Vyvanse in my case).
The part of Mounjaro that regulates the craving side of the weight loss equation (like reducing 'food noise' and the desire for sugary and fatty foods) seems to also affect other behaviors due to Mounjaro's effect on the brain's reward circuitry. I believe there are also early preliminary studies that indicate it can help with addictions like alcoholism.
Those drugs really are quite something. Shame they're so damn expensive. Insurance here in Germany is unfortunately legally prohibited from covering GLP-1 class drugs for weight loss unless you have a diabetes diagnosis.
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.
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.
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.
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.
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.
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?
> 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)
Bunch of longstanding vendors have had issues. SRY was one of the biggest names for direct-from-China, shipped peptides contaminated by disinfectant, caused severe reactions for some people. Nexaph is one of the biggest names now in the US, has tons of testing, etc., but got a batch a while back from whoever their manu is in China that had some unknown excipient that got played off as a "test formulation," etc.
Batch testing helps, but it requires the original lab to have actually adhered to the batches in a way that others can track, which isn't always the case. Sometimes top colors span multiple batches, tests on the vendor spreadsheet don't necessarily correspond to the batch being sold if you're trusting their testing, etc.
> Are there any testing/safety protocols that you follow?
Not much. I use a 22um PES filter into a cartridge and inject from it for a few weeks and call it a day. I don't even bother with my own testing at jano unless I have reason to believe something is off and need to confirm.
But I never got my LSD or DMT or anything tested before either so my risk tolerance is basically "eh, send it." I just can't in good conscience recommend people follow that same risk tolerance (though I won't begrudge adults the right to make informed decisions to inject basically anything they want into themselves, either.)
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
>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.
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.)
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.
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.
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?
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
> 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/)
Thanks. I'll admit I'm pretty surprised - my understanding is this sort of thing usually is a much bigger deal when it comes to fucking with things that impact FDA decisions, etc., so them publicly flouting it is pretty crazy to me.
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.
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.
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.
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.
> 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:
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.
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.
My psychiatrist is really interested in how it affects anxiety and depression as he has now seena number of improvements from a bunch of patients (including myself) who use the drug. Im on meds for both and only after i started on monjourno did i feel a signifigant change. The food cravings gone due to the nuerological effects but the stress levels lower as it seems to be impacting seratonin levels in ways as you increase dose.
The most surprising effect of Mounjaro, at least initially was that it drastically reduced by desire to drink beer, and when I started, my drinking was at a very unhealthy level (beer calories being a major factor in my weight problem). But maybe I'm an odd case, as I had a real beer habit but don't like wine and very rarely touched spirits.
Actually losing some weight as well as cutting my drinking down, helped me with depression far more than SSRIs (which had previously led to even faster weight gain)
Unfortunately, the effects started to diminish somewhat after about a year on it, as if I was building up a bit of a tolerance to the drug. And then I switched to Wegovy (=Ozempic) after big UK price hikes to Mounjaro, and found it much less effective, started gaining weight again (winter/xmas didn't help). Switching back to Mounjaro at the moment, but having to slowly step back up from a lower dose. Not expecting to see the initial near-miraculous effects again, expecting to have to combine it with some actual willpower and more exercise going forwards.
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!
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.
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.
> a number of improvements from a bunch of patients (including myself) who use the drug.
Does that include people who haven't lost weight on the drug? I imagine a lot of people will start to feel better when they look better and are healthier.
Semaglutide has a warning about not being suitable for folks with depression. I don't think I've seen any changes to my moods. I'm type-II bipolar and if anything my depression episodes are slightly worse now.
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
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.
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.
I always followed proper form and didn't ego lift, even though my deadlifts were the highest weight.
I think on retrospect deadlifts may have been my issue to, I did the deadlifts that day and later remember going to pickup something off the ground and getting the issue. Not sure if the deadlift was the cause, but I always thought my muscles were sore/tired and lax, thus when I went to lift the thing my lower back stability was compromised.
I'll try Romanian deadlifts and those other exercises, thanks for that suggestion.
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.
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."
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.
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.
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.
I have a bad disc, and while its still bad, a couple weeks of freestyle swimming workouts makes it not hurt for a year or two and lets me mountain bike comfortably again. Something to try if the usual stuff doesn't work, as it tends not to!
This was the disc between lumbar and sacrum. 1,000 ways to have a bad disc so results will vary a lot!
Funny, after semaglutide I developed moderate arthritis in my MTP(foot) joint.
I wonder if it was gout because it seemed to come on fast. They say semaglutide shouldn't cause gout but I'm not convinced. It has some very weird effects on my hydration. I drink a fair amount of water, but specifically at night I now have to urinate a dozen times throughout the night and wake up with my mouth almost dried shut.
I've lost 10% of my bodyweight(probably >1/3 muscle, sadly) which is great and it's taking the load off my joints, but man this foot thing is a bummer. I need to find a sports Dr because most foot docs seem to take the "just stop running/hiking and switch to biking/swimming" approach which doesn't work for me.
That kind of damage takes many years. Do you have scans from prior years? I also discovered I have arthritis in the ankle recently and there were no pain symptoms, only joint instability and issues higher up on the leg. This was probably caused by either genetics or ankle trauma from childhood that eventually reared its head in my 30s.
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.
GLP-1 and GIP are both hormones the human body makes in the gut. The famous drugs are mimicking those hormones. This is more akin to taking supplemental testosterone than it is to taking Fen-Phen or whatever.
Currently there is a torrent of research on the benefits of GLP1s. This raises doubts as most are not backed by solid hypothesis. The same happened almost a century earlier when aspirin was explored as super drug. A key metric is the NNT (number needed to treat), ie how many people should take the drug for one to meet the primary goal.
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.
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.
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
I have to chime in here. The full text is paywalled but if you have a subscription or institutional access the devil is in the details.
The "pilot study" the authors performed was an n=20 with 30% dropout, meaning 14 finished the study, 6/10 in the non-semaglutide arm and 8/10 in the semaglutide arm. They did not include participants who dropped out in their final analyses which is a big methodological flaw. I could go on about their choice in and measurement of outcomes, but suffice to say with only 14 participants these results should be taken with a grain of salt.
Further, they did extensive molecular biological studies in mice. There have been MANY (dozens) of murine (mouse) studies showing beneficial effects of various compounds / interventions on mouse knee osteoarthritis. None of them have translated into a therapy for the human disease. Mice live 2-3 years and have very different knee biomechanics than humans.
Appreciate the authors investigative efforts, but more confirmatory studies are needed before I'll be injecting semaglutide into my knee.
I wonder if the real problem is that we are really sick, and we just don't realize it: weight and eating too much processed food, so anything that improve these 2 aspects has also a lot of uncorrelated benefits.
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.
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
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.
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.
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.
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.
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.
At what point do we start to re-evaluate and re-test old assumptions about how much weight/caloric restriction impacts things? It seems unlikely that a molecule that slots into receptors in the pancreas also does something(?) to cardiac muscle [1], addiction [2], and now osteoarthritis(!).
This feels like a stretch to say that this happens independent of weight loss, and much more like we may have underestimated the impacts of weight loss on all of these other facets of life.
[1] - https://pmc.ncbi.nlm.nih.gov/articles/PMC12431743/
[2] - https://med.stanford.edu/news/insights/2025/04/ozempic-addic...
Similar reports have been ongoing about Metformin (another medication used for diabetes that causes weight loss and improves metabolic profile).
It's the simplest explanation that we have been underestimating just how unhealthy we are?
There's a synergy here, eat healthier, reduce blood sugar spikes, lose weight. And you are healthier than each individual effect alone would cause.
Maybe we're just ruining our bodies even if we don't put on weight by eating sugary foods that spoke our blood sugar. Or big meals that constantly make us switch into sit down and digest mode.
I'm open to something more happening but this isn't just GLPs. It seems we have uniquely attacked our bodies in a way that diabetes is the ultimate result but the entire journey is exquisitely toxic to our physiology.
Maybe fasting helps. Maybe keto helps. But this is similar to people who live off McDonalds suddenly go vegan and become healthy, is veganism that great? Or was the alternative for you just so awful for you?
> 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.
> 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...
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...
> 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.
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.
The article goes into a lot more depth than that and contains links to the peer-reviewed research that it is summarizing.
Exactly. Take 40Kgs off a person that weighs 150, and suddenly the cartilage in the joints get better. Go figure!
FTFA:
> By designing a precise diet-controlled setting to rule out the effect of appetite suppression and weight loss induced by SG, we demonstrate a weight loss-independent mechanism.
Hormones do a lot all over your body.
You're commenting on a paper that specifically found OA improvement without weight loss improvement...
> addition [2]
I had heard about the effects on addiction but this typo had me thinking there might be some effect on arithmetic ability, too.
sorry, fixed!
There's GLP-1 receptors in the brain, they induce neurogenesis
If they're not losing weight they're not restricting calories. Energy has to come from somewhere.
They explicitly controlled for all of this.
You can't mention CICO in this forum, where people have a unique genetic disorder that makes them "extract more calories from the food" or "burn way less" than other people, barring them of any personal responsibility about what they put in their mouth.
Why is that unlikely?
There are other known molecules that are many to many like cortisol, testosterone, and insulin.
I mean...if you read the paper they control for that.
Independent of weight loss, semaglutide (Ozempic) improves knee osteoarthritis by cartilage restoration, in both the mouse model and a small randomized clinical trial.
Old thinking was the benefit of GLP-1 drugs (like Ozempic) was solely from weight loss, however studies are showing there are other unique benefits. It's probably that semaglutide reduces inflammation allowing the body to repair and improves mitochondrial function in cartilage cells.
One thing I have noticed on Mounjaro is a (at least subjectively) significant decrease in impulse spending / buying random crap off Amazon. I have ADHD and that has been a real problem for quite a while - even with ADHD medication (Elvanse/Vyvanse in my case).
The part of Mounjaro that regulates the craving side of the weight loss equation (like reducing 'food noise' and the desire for sugary and fatty foods) seems to also affect other behaviors due to Mounjaro's effect on the brain's reward circuitry. I believe there are also early preliminary studies that indicate it can help with addictions like alcoholism.
Those drugs really are quite something. Shame they're so damn expensive. Insurance here in Germany is unfortunately legally prohibited from covering GLP-1 class drugs for weight loss unless you have a diabetes diagnosis.
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.
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?
> 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.
If you google "med spa arrest glp-1" you can find a good amount of occurrences, e.g. https://www.wsaz.com/2025/09/19/woman-arrested-selling-black...
> 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)
Bunch of longstanding vendors have had issues. SRY was one of the biggest names for direct-from-China, shipped peptides contaminated by disinfectant, caused severe reactions for some people. Nexaph is one of the biggest names now in the US, has tons of testing, etc., but got a batch a while back from whoever their manu is in China that had some unknown excipient that got played off as a "test formulation," etc.
Batch testing helps, but it requires the original lab to have actually adhered to the batches in a way that others can track, which isn't always the case. Sometimes top colors span multiple batches, tests on the vendor spreadsheet don't necessarily correspond to the batch being sold if you're trusting their testing, etc.
> Are there any testing/safety protocols that you follow?
Not much. I use a 22um PES filter into a cartridge and inject from it for a few weeks and call it a day. I don't even bother with my own testing at jano unless I have reason to believe something is off and need to confirm.
But I never got my LSD or DMT or anything tested before either so my risk tolerance is basically "eh, send it." I just can't in good conscience recommend people follow that same risk tolerance (though I won't begrudge adults the right to make informed decisions to inject basically anything they want into themselves, either.)
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.
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.
Possibly but it was from a family run company in Wales with a good reputation
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
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.
> 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.
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.
Yeah I was referring to what you have to do after taking a proper laxative
Try miralax yet? It’s basically tasteless in a glass of water.
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.
several years ago that might be true
in 2026 its... to quote South Park... "the rich get Ozympic, the poor get Body Positivity"
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.
My understanding is it's virtually impossible to overdose vitamin K (without injecting it anyway), and pretty difficult to do so with Vitamin D.
> 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.
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.
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?
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/Leadin...)
> 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-...)
Thanks. I'll admit I'm pretty surprised - my understanding is this sort of thing usually is a much bigger deal when it comes to fucking with things that impact FDA decisions, etc., so them publicly flouting it is pretty crazy to me.
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?
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.
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.
"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.
> 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.
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.
My psychiatrist is really interested in how it affects anxiety and depression as he has now seena number of improvements from a bunch of patients (including myself) who use the drug. Im on meds for both and only after i started on monjourno did i feel a signifigant change. The food cravings gone due to the nuerological effects but the stress levels lower as it seems to be impacting seratonin levels in ways as you increase dose.
The most surprising effect of Mounjaro, at least initially was that it drastically reduced by desire to drink beer, and when I started, my drinking was at a very unhealthy level (beer calories being a major factor in my weight problem). But maybe I'm an odd case, as I had a real beer habit but don't like wine and very rarely touched spirits.
Actually losing some weight as well as cutting my drinking down, helped me with depression far more than SSRIs (which had previously led to even faster weight gain)
Unfortunately, the effects started to diminish somewhat after about a year on it, as if I was building up a bit of a tolerance to the drug. And then I switched to Wegovy (=Ozempic) after big UK price hikes to Mounjaro, and found it much less effective, started gaining weight again (winter/xmas didn't help). Switching back to Mounjaro at the moment, but having to slowly step back up from a lower dose. Not expecting to see the initial near-miraculous effects again, expecting to have to combine it with some actual willpower and more exercise going forwards.
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!
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.
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.
> a number of improvements from a bunch of patients (including myself) who use the drug.
Does that include people who haven't lost weight on the drug? I imagine a lot of people will start to feel better when they look better and are healthier.
Semaglutide has a warning about not being suitable for folks with depression. I don't think I've seen any changes to my moods. I'm type-II bipolar and if anything my depression episodes are slightly worse now.
If you don't mind sharing, at what dose did you see positive impact on mood?
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
If it can somehow restore spinal disc function, I'm gonna start snorting the stuff.
I had a bulging lumbar disc - pure agony for 18 months. I had become used to carrying a lumbar pillow around with me everywhere I went. I couldn't lean forward for more than about 30 seconds without it being unbearable.
Then someone suggested I try dead hangs, stretching my hamstrings, and really cranking the McKenzie stretch. I'm not sure which one made the difference (all 3?), but pain was gone in 2 weeks.
Maybe it will help, maybe it won't. But since someone took a flyer telling me, I always share this with others in the small chance it helps them.
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.
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.
I always followed proper form and didn't ego lift, even though my deadlifts were the highest weight.
I think on retrospect deadlifts may have been my issue to, I did the deadlifts that day and later remember going to pickup something off the ground and getting the issue. Not sure if the deadlift was the cause, but I always thought my muscles were sore/tired and lax, thus when I went to lift the thing my lower back stability was compromised.
I'll try Romanian deadlifts and those other exercises, thanks for that suggestion.
I'm pretty much exclusively an RDL kind of guy these days but plenty of people go their whole lifting career being fine doing deadlifts.
I just don't like the stimulus to fatigue ratio for them and spend more time with cables, machines, and dumbbells than barbells these days.
Do you have any links for how you did these stretches? I know someone that could do with trying this.
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.
Thanks for the reply, will pass this info on.
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."
Can you give some examples of immune overreach that are improved?
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.
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.
I know you're getting a lot of "this worked for me" responses and I wanted to throw one more in. I used to have lower back problems all the time, but after following a strength training program for the olympic lifts with a personal trainer, generally the only time I have lower back pain now is if I've gone too hard to deadlifts or rows, not from general day to day things.
SW033291 or MF-300 might be interesting to look out for with spinal function. https://www.sciencedaily.com/releases/2026/01/260120000333.h...
I have a bad disc, and while its still bad, a couple weeks of freestyle swimming workouts makes it not hurt for a year or two and lets me mountain bike comfortably again. Something to try if the usual stuff doesn't work, as it tends not to!
This was the disc between lumbar and sacrum. 1,000 ways to have a bad disc so results will vary a lot!
Funny, after semaglutide I developed moderate arthritis in my MTP(foot) joint.
I wonder if it was gout because it seemed to come on fast. They say semaglutide shouldn't cause gout but I'm not convinced. It has some very weird effects on my hydration. I drink a fair amount of water, but specifically at night I now have to urinate a dozen times throughout the night and wake up with my mouth almost dried shut.
I've lost 10% of my bodyweight(probably >1/3 muscle, sadly) which is great and it's taking the load off my joints, but man this foot thing is a bummer. I need to find a sports Dr because most foot docs seem to take the "just stop running/hiking and switch to biking/swimming" approach which doesn't work for me.
That kind of damage takes many years. Do you have scans from prior years? I also discovered I have arthritis in the ankle recently and there were no pain symptoms, only joint instability and issues higher up on the leg. This was probably caused by either genetics or ankle trauma from childhood that eventually reared its head in my 30s.
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.
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...
Fulltext: https://gwern.net/doc/longevity/glp/semaglutide/2026-qin.pdf
GLP-1 and GIP are both hormones the human body makes in the gut. The famous drugs are mimicking those hormones. This is more akin to taking supplemental testosterone than it is to taking Fen-Phen or whatever.
Currently there is a torrent of research on the benefits of GLP1s. This raises doubts as most are not backed by solid hypothesis. The same happened almost a century earlier when aspirin was explored as super drug. A key metric is the NNT (number needed to treat), ie how many people should take the drug for one to meet the primary goal.
Most of the results here are in mice, but they apparently did a small pilot study in humans:
https://www.chictr.org.cn/showprojEN.html?proj=176336
To the extent that there are results, they're paywalled. But, oddly, the entire article appears to be posted in the supplemental information section:
https://www.cell.com/cms/10.1016/j.cmet.2026.01.008/attachme...
From Figure 1, the effect size in mice was fairly large.
Pages 9 and 10 give a very brief description of the human trial. It looks like they did not make any effort to disentangle effects due to weight loss from effects independent of weight loss in humans. The humans in the study group had a 17% increase in knee cartilage thickness, and the dose used was (see page e3):
"Participants receiving SG treatment initiated with a dose of 0.25 mg in the first week, and increased the dose in a stepwise manner each subsequent week until reaching the target dose of 0.5 mg/week (incremental steps of 0.125 mg)."
AIUI this matches the current recommended starting dosage for diabetes and is considerably lower than the dosages used for weight loss.
There are other clinical trials, such as one for Orforglipron, which are also studying this specifically.
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.
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
I have to chime in here. The full text is paywalled but if you have a subscription or institutional access the devil is in the details.
The "pilot study" the authors performed was an n=20 with 30% dropout, meaning 14 finished the study, 6/10 in the non-semaglutide arm and 8/10 in the semaglutide arm. They did not include participants who dropped out in their final analyses which is a big methodological flaw. I could go on about their choice in and measurement of outcomes, but suffice to say with only 14 participants these results should be taken with a grain of salt.
Further, they did extensive molecular biological studies in mice. There have been MANY (dozens) of murine (mouse) studies showing beneficial effects of various compounds / interventions on mouse knee osteoarthritis. None of them have translated into a therapy for the human disease. Mice live 2-3 years and have very different knee biomechanics than humans.
Appreciate the authors investigative efforts, but more confirmatory studies are needed before I'll be injecting semaglutide into my knee.
I wonder if the real problem is that we are really sick, and we just don't realize it: weight and eating too much processed food, so anything that improve these 2 aspects has also a lot of uncorrelated benefits.
We don’t see lots of stories about how dieting causes cartilage to grow back.
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.
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
I'm always wary of such claims as it is not unusual for companies to extend the use of their drugs, after all the patent expires in some years
I have a friend who was put on a GLP-1 and had an astonishing reduction in arthritis pain.
Typo in the title - “independant”
I hope this goes through clinical trials before my joints degrade completely
is Big Pharma going to invest in any of the other peptides or is it just one and done?
because the underground grey market seems to be snowballing for all kinds of diseases and symptoms
just very dangerous without any regulation
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.
It seems like pharma developed many of them, but it takes a while to get them to market.
Title is misspelled, should be “independent”.
did anyone actually read the article to figure out if these results are at all reliable?
Why are studies on mice so popular on HN?
Ok it makes sense now. This is fasting.
yes and ramadan is coming lets do the fasting and get healthier :) it is a little bit long but we will see
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.
It's a good idea. There are many studied benefits to (intermittent) fasting, for example: https://pmc.ncbi.nlm.nih.gov/articles/PMC11262566/
You think fasting improves knee osteoarthritis independent of weight loss?
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.
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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.
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.
Good point. Perhaps if you take them for 40 years, you become biologically immortal. Who can really say?
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.
Okay I confess to getting taken by this comment. I downvoted and retracted. Sometimes sarcasm is too close to widely held beliefs.
I can't tell if this is a sarcastic response in bad taste, or if it's an authentic, if misguided, opinion.
the new ivermectin...