Usual rant to news outlets: Cite your damn sources! (if they are public, which is the case here). This is a web page, not printed paper, web pages support links, links are not just for ads!
I understand not having a link to the primary source at the top of an article because you might be trying to write an explainer, but if you want to avoid confusing your readers but still do the right thing at the very least include a bunch of source links at the bottom of the article!
I know all the cynical reasons not to do it, but I feel like even the good faith objection has a pretty straightforward solution.
Will there be a large-dose trial? I imagine that’s going to be more difficult, as the weight-loss effect of GLP-1 means you cant include frail patients in your target group. And GLP-1 at high doses also has some unfavourable side-effects: nausea, vomiting, diarrhea, constipation.
I'm surprised this study didn't segment a portion of the subjects as diabetic and I wonder if such a sub-group would potentially have seen an improvement over non-diabetic subjects.
I'm sure this isn't the last we will hear of the potential of GLP1s in neurological diseases.
At the same time, our work in neurostimulation of slow-wave sleep is showing promise with a correlation between neurostimulation response, amyloid response, and memory in healthy older adults[1], as well as tolerance of stimulation in people living with Alzheimer's [2].
More studies to be done, but if you're curious, we link to a large body of research on our website https://www.affectablesleep.com/how-it-works?type=All#resear...
Why would Ozempic, a chemical affecting a specific receptor found in specific parts of the body, affect alzheimer's? I'm just asking questions here I don't understand what the mechanism of action is that this would be disappointing news.
Semaglutide (Ozempic) has potential therapeutic effects in neurodegenerative disorders through "modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis". It has shown benefits in animal models of Alzheimer's and Parkinson's. So they're not just testing a random drug, but something that could work.
I know we can tell that a chemical does a particular thing in the body, but can we tell that it does not do anything other than that thing? The body is ridiculously complex, and as far as I know we don’t know how every part (or combination of parts) works.
Edit: I mean in the theoretical “this targets the x receptor” kind of way, not in “we tested this and found no causal link” way.
That's why I'm genuinely asking why this would be disappointing, like what was the evidence that this does affect Alzheimer's. You would expect by X does not affect Y by default, so clearly there had to be a theory why you'd spend 2 years on a study to rule it out.
Significant, sustained weight loss can prevent or reduce the effects of conditions known to increase the likelihood or hasten the onset of Alzheimer's, like diabetes and high blood pressure.
This is anecdotal, I don't have proof but it's something I think is somewhat related. Is that obesity and nuerodegenerative diseases are somewhat related. So that's a guess as to why some people might have though a weight loss drug would potentially be related in some way with alzheimers.
This could just be false though, I can't recall where I heard this information. So do some searching before quoting me.
Personally, living with two T1D ( type 1 insulin dependent diabetic, the autoimmune disease not to be confused with the i am old, fat and over eat disorder) when your blood sugar is too high or low , you act weird , you are in a fog . Long term effects of the swings and sustained levels cause brain damage, not necessarily traumatic brain injuries but damage nonetheless.
So i can see the correlation for T1D and undiagnosed T2D cases Alzheimers. Now having a parent with both T2D and Alzheimers when they were taking rebelsis there was a change in their overall mood and activity , but i saw the change was "hey your sugar is under control, and no i am not your buddy from the army" . To be clear the difference is the fog of being unclear about what's going on like you're drunk , vs the grand delusions of seeing a different person that's not there .
This should have been obvious for the researchers.
As I understand it, one of the reasons GLP-1 agonists seem to affect so many different things is that evolutionarily, it does not seem at all surprising that a huge number of things are hooked on the hungry/full signal.
I kind of think if it fixes a fundamental issue - too much weight.
Another problem it seems to help with is addictive/impulsive behavior. This might lead to wrong choices in diet or activity.
I suspect that many many functions of the body are degraded or disabled by too much weight or wrong choices, and fixing those problems might let the body cure and maintain itself properly.
Obesity may increase the risk of Alzheimer's but it's far from a requirement for the disease. I can't find a link between Alzheimer's and being overweight except in case of obesity.
Generally this is the answer when there's an announcement like this. Some early paper or analysis showed some (often weak but potentially very interesting) correlation between $new_drug and $scary_disease/$scary_disorder. Doctors and scientists go off and study that in more depth with better controls or more data points and we learn a little more about the world, if you miss the initial paper(s) the follow up can seem a little random.
This new study that did not find a causal link was part of the attempt to find out how. The original study was more of an observation than a deep dive.
You could think of it similar to a study that shows something like "People who don't watch network TV have fewer strokes", which could be an interesting correlation, but the causal effect might be something more like "people who are more health conscious tend to avoid sitting down for extended waking periods" which ultimately has nothing to do with TV.
The article describes data showing a correlation between Ozempic use and slowed progression of certain brain conditions. The study aimed to determine whether that effect came from Ozempic itself or simply from weight loss. Once researchers controlled for weight loss, the effect disappeared. In other words, correlation, not causation.
That's an important caveat. But effectively it sounds like Ozempic typically results in a better diet, and a better diet typically results in slowed progression.
It's disappointing to the manufacturers and consumers because many boomers are taking it already to treat 40+ years of poor and/or indulgent consumption (and more will now that they've negotiated a price reduction).
Glp-1 drugs inhibit drinking and compulsive behaviors and I'm not sure the mechanism of action is known
involves vascular inflammation. in the brain in the case of alzheimers. <theorized.> more readily applicable to vascular dementia.
and then, in the rest of the cardiovascular system in artherosclerosis/CVD. (reducing inflammation = reducing plaques laid down over them , that are being attracted to inflamed areas..
or piling up dead macrophages and foamy cells that went there to help.)
im not aware that either of these are totally settled at this time other than some anecdotal data on slowing down MACE and progression in the latter case (CVD). some cardiologists are believers and incorporating it in treatment now. its not an industry best practice but for those who are prescribing it for this reason, theyre citing a 20-40% reduction in events over 2-5 years.
or put another way. we know inflammation plays a role in CVD and we have a pretty reliable biomarker (CRP ) for whether this holds water and the inflammation is reduced by glp-1 agonists. not to be controversial or speak to medical matters but its my understanding that it does.
its role in dementia/alzheimers is just one of the ideas out there but the reasoning and the conclusions are kind of in the same neighborhood.
I would think eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits. Which should be perfectly fine as its valid and results in massive positives in both health and quality of life.
We already know that's not the case though. A huge portion of the benefits are downstream of obesity, yes, but we already know GLPs have positive effects even without weight loss.
genuinely curious if you have some sources I can read on the subject? most of the benefits/papers I've seen have not touched on or included studies for patients on GLP's where weight loss was ruled out as the factor?
Actually even in the very beginning I saw numerous studies showing effects outside weight loss, I'm sure a search would find them. I remember seeing at least 3-4 a couple years ago.
It is a reasonable thought, but that exact question has been investigated and benefits were not totally explained by weight loss. I don't recall the link, but it was featured on HN
>eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits.
This is not true.
Ozempic appears to affect the brain's rewards system and its known to decreased cravings and urges for a range of unhealthy behaviors, from alcohol consumption and smoking to gambling and shopping to nail biting and skin picking.
Beyond that, Ozempic appears to lower the risk of heart attacks and strokes in overweight people well beyond what weight loss alone would explain. Maybe due to the above (less drinking and smoking) or another unknown mechanism of action.
I started taking prescription Zepbound (tirzepatide) right when it was approved for about 6 months and lost 30 pounds, later switched to a low dose of much cheaper grey market semaglutide for maintenance. The anti-drinking side effect was unexpected and somewhat shocking to experience. I had heavily drank in the evening for almost a decade to varying degrees and then pretty much stopped overnight once hitting the 5mg dose of Zepbound on the second month.
After ending the Zepbound I had a few months where I wasn't taking anything before resuming the maintenance semaglutide, and although food cravings slowly started returning, I still had/have zero interest in drinking whatsoever unless in a social setting where I may have 1-2 drinks (but usually avoid it altogether without requiring any conscious effort).
There is definitely massive variance in the individual psychology/biology that leads to habitual alcohol overuse so I'm sure others might not have the same experience. But for me I'm pretty confident that breaking that deeply engrained habit of starting the first of 6-10 drinks at 6-7pm every day was what did it (without feeling like I was being forced to do something I didn't want). Which was pretty much impossible for me to even envision back when it was such a normal part of my day-to-day coping strategy for stress/depression/etc.
Although I always knew my drinking was excessive and terrible for my health, past my early 20s I was super high functioning and wasn't interfering with my job or life (other than holding me back and probably slowly killing me), and so being an "alcoholic" was never part of my identity (rightly or wrongly), which I kinda think ironically made it easier to just take the win and move on with my life without nagging self-doubt or fixation on whether my "addiction is cured".
But it's been about 2 years now and I hardly ever think about alcohol even when super stressed so something, somewhere in my brain changed thanks to tirzepatide and whatever the mechanism I'm grateful for that happy accident of a positive side effect!
> later switched to a low dose of much cheaper grey market semaglutide for maintenance.
Do you plan on staying on a 'low dose' of semaglutide Ad vitam æternam ?
I'm asking because I believe that's one of the negative of these kind of drugs, it's effective at losing weight but as soon as you stop you gain back all the weight whereas learning to eat healthy is slower but more durable.
I remember I saw a meta review that claimed in the abstract that "analysis showed a rapid regain of weight after cessation of therapy", but then looking into it deeper actually quite a bit of weight loss was retained even many months after stopping.
In my personal experience I've now known about 12 people who've taken it and stopped, and none have "rapidly" regained, in fact many have retained most of their loss for significant periods of time. Most people gain weight over a long period of time (from lets say early teen to their current age).
What happens when they stop is a very slow return to baseline gain. So if it took them 10 years to become obese, then it takes 6-12 months to lose it all with Tirzepatide, you'd expect it would take them 10 years again to regain it.
People act like this is some sort of addiction, but I don't think so - and I'd bet that a "refresher" that was only a small % of the year would keep most people completely at baseline, and they could even slowly taper that down.
For me at least it definitely wasn't quite so abrupt, it was probably about 2.5 months before I noticed the trend line ever so slowly moving up. Pre-Zepbound I had already lost about 30 pounds from my max weight of 260ish thanks to a strict Keto diet I began at the beginning of COVID lockdowns which was a lot of effort to maintain long term, so when I saw I met the criteria for my insurance to cover Zepbound I was like "sure, why not?".
I'd probably just go back to Keto if I decided or was forced to stop a GLP-1a completely. Keto was the first and only way I've had success losing weight in my life. But once the initial novelty wears off it takes a lot of discipline to stick to and continually avoid the pressure from friends/family to eat with everyone else. I'm also vaguely concerned about cholesterol impact long term doing it for life, but relative to obesity probably still a good trade off.
It's definitely doable though, I did it for 2 years so I know the drill and that's my fallback. But not being obese is much more enjoyable than being obese, and it's a lot easier to exercise at a normal weight, so I don't have much interest in going back to 260 pounds. If that meant taking a drug for life, so be it unless it turns out to cause turbo-cancer or something.
I mostly eat "healthy" foods by preference (and habit from growing up in a "health food" family), but for me my problem is managing portion control while never feeling completely full at the target calories per meal/day. Which can feel pretty miserable to stick with especially comparing to others in my family who more or less eat the same foods but don't have that problem at all. Keto was so effective because I actually felt "full" (at the expense of excluding a lot of otherwise healthy but carb-rich foods).
Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.
> Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.
Well I always assumed that people are fat because they are eating too much...of the wrong thing.
I lost 10kg not long ago, 20 lbs in American, and never ever i did feel hungry. Quite the opposite, i would be stuffed to the nose on fruits, vegetables and meats.
And believe me when I tell you I ate like an ogre.
I challenge anyone to actually gain weight on eating only vegetable fruits and meat. After losing these 10kg, I tried to gain 15kg of muscle and overeat on this regime to the point to want to vomit, couldn't gain weight. When I added fat and cereals, weight increased so fast I had to slow down.
With the average caloric expenditure being 2200 kcal for a normal healthy man, not even doing sport, the average vegetable being 300 kcal per kg, it means you would have to eat 7.3kg (16lbs) of vegetable per day.
I don't know you personally but I can safely say that you can't eat 16 lbs of vegetable per day, or 5lbs per meal. It's physically impossible.
So yeah I guess that how people experience hunger/starvation could play a role, but it's not the full story.
A couple years before starting Zepbound I had tried a prescription for naltrexone for 3 or 4 months to reduce drinking which had pretty much zero effect for me. Naltrexone apparently helps for some people and has a similar theorized mechanism acting on reward/pleasure but didn't do anything to break that habit of pouring a drink within the first hour I was back home.
I might have drank slightly less as it was slightly less enjoyable but did nothing for the habitual element which for me was much more problematic than how the alcohol made me "feel" subjectively or the exact number of drinks I had per night.
This is probably unrelated, but I used to play a lot of DotA for years (at some points for 12 hours a day), then quit cold turkey, then started again last year, but maybe 30-60 minutes a day.
After I started Mounjaro, I haven't really had the urge to play at all. I played a game a few weeks ago but I was kind of "meh" about it, and haven't played since. It's striking.
Making stuff, big time. I love making things with hardware, software, or 3D printing.
A few friends and I made a maker community, and over the weekend I made a semi-automated newsletter for links we post in our Discord (https://themakery.cc). I really had fun doing that, it was great.
Nah, obesity reduction is itself a downstream effect of messing with neurotransmitters. There have to be other consequences of that - both good and bad.
There don't have to be any other consequences, certainly not both good and bad ones. Biology doesn't actually have some scale of justice that means good things must be offset by bad things.
But yes, it's very probable (in fact we already know) the drug is doing several things in the body.
I was more thinking that evolved systems rarely have convenient switches you can flip and just get a single outcome. You perturb the system, and you get a cascade of changes. It's not like engineering.
Nothing about justice was implied, so lets say desirable and undesirable instead of good and bad.
Alzheimer's isn't one thing but a category of degenerative pathologies.
Probably also requires holistic improvements in lifestyle ( hydration, sleep, exercise, diet (not just quantity)), gene in/activation, &| vaccines for TAU &| β-amyloid.
PS: I wonder if nootropics will be developed to emulate or enhance the effects of exercise.
Source: https://www.novonordisk.com/news-and-media/news-and-ir-mater...
Ongoing study: https://pubmed.ncbi.nlm.nih.gov/39780249/
Usual rant to news outlets: Cite your damn sources! (if they are public, which is the case here). This is a web page, not printed paper, web pages support links, links are not just for ads!
I understand not having a link to the primary source at the top of an article because you might be trying to write an explainer, but if you want to avoid confusing your readers but still do the right thing at the very least include a bunch of source links at the bottom of the article!
I know all the cynical reasons not to do it, but I feel like even the good faith objection has a pretty straightforward solution.
But but but we have to keep traffic on our website! Engagement!
That's why when you click on a link you see 1/10th of the article, and then a video, and 3 other irrelevant inlays for other links.
Oh and the video auto plays with sound.
And every word in the article that is remotely a 'tag' links to other parts of the website.
> video auto plays with sound.
Without sound in Firefox, I assume?
I can't remember the source, but I think this only rules out small-dose, oral. There will still be a trial with large-dose, injectable.
Will there be a large-dose trial? I imagine that’s going to be more difficult, as the weight-loss effect of GLP-1 means you cant include frail patients in your target group. And GLP-1 at high doses also has some unfavourable side-effects: nausea, vomiting, diarrhea, constipation.
Indeed, and it's literally not Ozempic but Rybelsus.
For reference in typical maintenance doses:
- Rybelsus (type-2 diabetes; oral semaglutide 14 mg/day; much less bioavailability)
- Wegovy (obesity; injectable semaglutide 2.4 mg/wk)
- Ozempic (type-2 diabetes; injectable semaglutide 1.0 mg/wk)
I'm surprised this study didn't segment a portion of the subjects as diabetic and I wonder if such a sub-group would potentially have seen an improvement over non-diabetic subjects.
I'm sure this isn't the last we will hear of the potential of GLP1s in neurological diseases.
At the same time, our work in neurostimulation of slow-wave sleep is showing promise with a correlation between neurostimulation response, amyloid response, and memory in healthy older adults[1], as well as tolerance of stimulation in people living with Alzheimer's [2]. More studies to be done, but if you're curious, we link to a large body of research on our website https://www.affectablesleep.com/how-it-works?type=All#resear...
[1] https://doi.org/10.1093/ageing/afad228 [2] https://doi.org/10.1016/j.jagp.2024.07.002
Why would Ozempic, a chemical affecting a specific receptor found in specific parts of the body, affect alzheimer's? I'm just asking questions here I don't understand what the mechanism of action is that this would be disappointing news.
Semaglutide (Ozempic) has potential therapeutic effects in neurodegenerative disorders through "modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis". It has shown benefits in animal models of Alzheimer's and Parkinson's. So they're not just testing a random drug, but something that could work.
For details, see: https://pubmed.ncbi.nlm.nih.gov/38921025
This diagram shows how Ozempic can produce these results, the various pathways from the GLP-1 receptor to reduce inflammation, protect neurons, and affect mitochondria: https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87c0/11202139/72234dd...
Thank you, I really appreciate it, as I'm not educated in biochem at all.
"Type 3 diabetes" is one of the speculated causes of alzheimer's. The evidence there is not great.
Fixing type 1 or 2 diabetes does not fix the damage they already did either.
I know we can tell that a chemical does a particular thing in the body, but can we tell that it does not do anything other than that thing? The body is ridiculously complex, and as far as I know we don’t know how every part (or combination of parts) works.
Edit: I mean in the theoretical “this targets the x receptor” kind of way, not in “we tested this and found no causal link” way.
That's why I'm genuinely asking why this would be disappointing, like what was the evidence that this does affect Alzheimer's. You would expect by X does not affect Y by default, so clearly there had to be a theory why you'd spend 2 years on a study to rule it out.
Significant, sustained weight loss can prevent or reduce the effects of conditions known to increase the likelihood or hasten the onset of Alzheimer's, like diabetes and high blood pressure.
This is anecdotal, I don't have proof but it's something I think is somewhat related. Is that obesity and nuerodegenerative diseases are somewhat related. So that's a guess as to why some people might have though a weight loss drug would potentially be related in some way with alzheimers.
This could just be false though, I can't recall where I heard this information. So do some searching before quoting me.
Obesity often goes hand in hand with poorly regulated blood sugar and high blood pressure, both known risk factors for Alzheimer's.
Ozempic is a diabetes drug, and there's a hypothesis that Alzheimer's is really a form of diabetes.
Personally, living with two T1D ( type 1 insulin dependent diabetic, the autoimmune disease not to be confused with the i am old, fat and over eat disorder) when your blood sugar is too high or low , you act weird , you are in a fog . Long term effects of the swings and sustained levels cause brain damage, not necessarily traumatic brain injuries but damage nonetheless.
So i can see the correlation for T1D and undiagnosed T2D cases Alzheimers. Now having a parent with both T2D and Alzheimers when they were taking rebelsis there was a change in their overall mood and activity , but i saw the change was "hey your sugar is under control, and no i am not your buddy from the army" . To be clear the difference is the fog of being unclear about what's going on like you're drunk , vs the grand delusions of seeing a different person that's not there .
This should have been obvious for the researchers.
T2D is not limited to "old, fat overeaters".
> This should have been obvious for the researchers.
That's why they do research, to find out instead of just guessing.
As I understand it, one of the reasons GLP-1 agonists seem to affect so many different things is that evolutionarily, it does not seem at all surprising that a huge number of things are hooked on the hungry/full signal.
It appears that it might be even more generically the "need/satiated" signal.
Maybe because poor diet has been linked to alzheimers?
I kind of think if it fixes a fundamental issue - too much weight.
Another problem it seems to help with is addictive/impulsive behavior. This might lead to wrong choices in diet or activity.
I suspect that many many functions of the body are degraded or disabled by too much weight or wrong choices, and fixing those problems might let the body cure and maintain itself properly.
Obesity may increase the risk of Alzheimer's but it's far from a requirement for the disease. I can't find a link between Alzheimer's and being overweight except in case of obesity.
https://www.alzheimers.org.uk/about-dementia/managing-the-ri...
It was correlated to lower Dementia rates in a past study. https://journals.sagepub.com/doi/10.1177/13872877251351329
Thanks, I wasn't aware of this. Do we know how?
Generally this is the answer when there's an announcement like this. Some early paper or analysis showed some (often weak but potentially very interesting) correlation between $new_drug and $scary_disease/$scary_disorder. Doctors and scientists go off and study that in more depth with better controls or more data points and we learn a little more about the world, if you miss the initial paper(s) the follow up can seem a little random.
I don't think there's a confirmed mechanism (or even whether the fact that it does prevent dementia is a confirmed fact).
But you could speculate that obesity -> cardiovascular issues -> neurological damage, and that could explain things.
We don't know the "how" in a surprising number of medicines.
We unfortunate know very little about how dementia / Alzheimer's develop in the first place.
This new study that did not find a causal link was part of the attempt to find out how. The original study was more of an observation than a deep dive.
You could think of it similar to a study that shows something like "People who don't watch network TV have fewer strokes", which could be an interesting correlation, but the causal effect might be something more like "people who are more health conscious tend to avoid sitting down for extended waking periods" which ultimately has nothing to do with TV.
I read this[1] some time ago. Seems relevant now.
- [1] https://www.astralcodexten.com/p/why-does-ozempic-cure-all-d...
The article describes data showing a correlation between Ozempic use and slowed progression of certain brain conditions. The study aimed to determine whether that effect came from Ozempic itself or simply from weight loss. Once researchers controlled for weight loss, the effect disappeared. In other words, correlation, not causation.
That's an important caveat. But effectively it sounds like Ozempic typically results in a better diet, and a better diet typically results in slowed progression.
Since Ozempic was the primary reason for the weight loss, it's still causation. Although indirect.
A lot of medical research is "x is correlated with y and we have no idea why".
"Alleged magic cure does not solve all our problems" just isn't as catchy.
It's disappointing to the manufacturers and consumers because many boomers are taking it already to treat 40+ years of poor and/or indulgent consumption (and more will now that they've negotiated a price reduction).
Glp-1 drugs inhibit drinking and compulsive behaviors and I'm not sure the mechanism of action is known
What about vascular dementia?
the premise , iirc:
involves vascular inflammation. in the brain in the case of alzheimers. <theorized.> more readily applicable to vascular dementia.
and then, in the rest of the cardiovascular system in artherosclerosis/CVD. (reducing inflammation = reducing plaques laid down over them , that are being attracted to inflamed areas.. or piling up dead macrophages and foamy cells that went there to help.)
im not aware that either of these are totally settled at this time other than some anecdotal data on slowing down MACE and progression in the latter case (CVD). some cardiologists are believers and incorporating it in treatment now. its not an industry best practice but for those who are prescribing it for this reason, theyre citing a 20-40% reduction in events over 2-5 years.
or put another way. we know inflammation plays a role in CVD and we have a pretty reliable biomarker (CRP ) for whether this holds water and the inflammation is reduced by glp-1 agonists. not to be controversial or speak to medical matters but its my understanding that it does.
its role in dementia/alzheimers is just one of the ideas out there but the reasoning and the conclusions are kind of in the same neighborhood.
I would think eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits. Which should be perfectly fine as its valid and results in massive positives in both health and quality of life.
We already know that's not the case though. A huge portion of the benefits are downstream of obesity, yes, but we already know GLPs have positive effects even without weight loss.
genuinely curious if you have some sources I can read on the subject? most of the benefits/papers I've seen have not touched on or included studies for patients on GLP's where weight loss was ruled out as the factor?
https://www.medlink.com/news/from-blood-sugar-to-brain-relie...
Actually even in the very beginning I saw numerous studies showing effects outside weight loss, I'm sure a search would find them. I remember seeing at least 3-4 a couple years ago.
It is a reasonable thought, but that exact question has been investigated and benefits were not totally explained by weight loss. I don't recall the link, but it was featured on HN
>eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits.
This is not true.
Ozempic appears to affect the brain's rewards system and its known to decreased cravings and urges for a range of unhealthy behaviors, from alcohol consumption and smoking to gambling and shopping to nail biting and skin picking.
Beyond that, Ozempic appears to lower the risk of heart attacks and strokes in overweight people well beyond what weight loss alone would explain. Maybe due to the above (less drinking and smoking) or another unknown mechanism of action.
https://www.scientificamerican.com/article/weight-loss-drug-...
I started taking prescription Zepbound (tirzepatide) right when it was approved for about 6 months and lost 30 pounds, later switched to a low dose of much cheaper grey market semaglutide for maintenance. The anti-drinking side effect was unexpected and somewhat shocking to experience. I had heavily drank in the evening for almost a decade to varying degrees and then pretty much stopped overnight once hitting the 5mg dose of Zepbound on the second month. After ending the Zepbound I had a few months where I wasn't taking anything before resuming the maintenance semaglutide, and although food cravings slowly started returning, I still had/have zero interest in drinking whatsoever unless in a social setting where I may have 1-2 drinks (but usually avoid it altogether without requiring any conscious effort).
There is definitely massive variance in the individual psychology/biology that leads to habitual alcohol overuse so I'm sure others might not have the same experience. But for me I'm pretty confident that breaking that deeply engrained habit of starting the first of 6-10 drinks at 6-7pm every day was what did it (without feeling like I was being forced to do something I didn't want). Which was pretty much impossible for me to even envision back when it was such a normal part of my day-to-day coping strategy for stress/depression/etc.
Although I always knew my drinking was excessive and terrible for my health, past my early 20s I was super high functioning and wasn't interfering with my job or life (other than holding me back and probably slowly killing me), and so being an "alcoholic" was never part of my identity (rightly or wrongly), which I kinda think ironically made it easier to just take the win and move on with my life without nagging self-doubt or fixation on whether my "addiction is cured".
But it's been about 2 years now and I hardly ever think about alcohol even when super stressed so something, somewhere in my brain changed thanks to tirzepatide and whatever the mechanism I'm grateful for that happy accident of a positive side effect!
> later switched to a low dose of much cheaper grey market semaglutide for maintenance.
Do you plan on staying on a 'low dose' of semaglutide Ad vitam æternam ?
I'm asking because I believe that's one of the negative of these kind of drugs, it's effective at losing weight but as soon as you stop you gain back all the weight whereas learning to eat healthy is slower but more durable.
I remember I saw a meta review that claimed in the abstract that "analysis showed a rapid regain of weight after cessation of therapy", but then looking into it deeper actually quite a bit of weight loss was retained even many months after stopping.
In my personal experience I've now known about 12 people who've taken it and stopped, and none have "rapidly" regained, in fact many have retained most of their loss for significant periods of time. Most people gain weight over a long period of time (from lets say early teen to their current age).
What happens when they stop is a very slow return to baseline gain. So if it took them 10 years to become obese, then it takes 6-12 months to lose it all with Tirzepatide, you'd expect it would take them 10 years again to regain it.
People act like this is some sort of addiction, but I don't think so - and I'd bet that a "refresher" that was only a small % of the year would keep most people completely at baseline, and they could even slowly taper that down.
For me at least it definitely wasn't quite so abrupt, it was probably about 2.5 months before I noticed the trend line ever so slowly moving up. Pre-Zepbound I had already lost about 30 pounds from my max weight of 260ish thanks to a strict Keto diet I began at the beginning of COVID lockdowns which was a lot of effort to maintain long term, so when I saw I met the criteria for my insurance to cover Zepbound I was like "sure, why not?".
I'd probably just go back to Keto if I decided or was forced to stop a GLP-1a completely. Keto was the first and only way I've had success losing weight in my life. But once the initial novelty wears off it takes a lot of discipline to stick to and continually avoid the pressure from friends/family to eat with everyone else. I'm also vaguely concerned about cholesterol impact long term doing it for life, but relative to obesity probably still a good trade off.
It's definitely doable though, I did it for 2 years so I know the drill and that's my fallback. But not being obese is much more enjoyable than being obese, and it's a lot easier to exercise at a normal weight, so I don't have much interest in going back to 260 pounds. If that meant taking a drug for life, so be it unless it turns out to cause turbo-cancer or something.
I mostly eat "healthy" foods by preference (and habit from growing up in a "health food" family), but for me my problem is managing portion control while never feeling completely full at the target calories per meal/day. Which can feel pretty miserable to stick with especially comparing to others in my family who more or less eat the same foods but don't have that problem at all. Keto was so effective because I actually felt "full" (at the expense of excluding a lot of otherwise healthy but carb-rich foods).
Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.
> Taking Zepbound definitely reshaped my perception of obesity though, compared to Keto which required constant, intense self-enforced discipline avoiding 4/5 of any menu, being on a GLP1-a and able to eat what everyone else is eating but just stop and not feel hunger pains or cravings convinced me the attitude of "fat=lacking discipline" is antiquated and ignores real variance in how different people experience hunger/satiation.
Well I always assumed that people are fat because they are eating too much...of the wrong thing.
I lost 10kg not long ago, 20 lbs in American, and never ever i did feel hungry. Quite the opposite, i would be stuffed to the nose on fruits, vegetables and meats.
And believe me when I tell you I ate like an ogre.
I challenge anyone to actually gain weight on eating only vegetable fruits and meat. After losing these 10kg, I tried to gain 15kg of muscle and overeat on this regime to the point to want to vomit, couldn't gain weight. When I added fat and cereals, weight increased so fast I had to slow down.
With the average caloric expenditure being 2200 kcal for a normal healthy man, not even doing sport, the average vegetable being 300 kcal per kg, it means you would have to eat 7.3kg (16lbs) of vegetable per day.
I don't know you personally but I can safely say that you can't eat 16 lbs of vegetable per day, or 5lbs per meal. It's physically impossible.
So yeah I guess that how people experience hunger/starvation could play a role, but it's not the full story.
(too late to edit but I forgot to include)
A couple years before starting Zepbound I had tried a prescription for naltrexone for 3 or 4 months to reduce drinking which had pretty much zero effect for me. Naltrexone apparently helps for some people and has a similar theorized mechanism acting on reward/pleasure but didn't do anything to break that habit of pouring a drink within the first hour I was back home.
I might have drank slightly less as it was slightly less enjoyable but did nothing for the habitual element which for me was much more problematic than how the alcohol made me "feel" subjectively or the exact number of drinks I had per night.
This is probably unrelated, but I used to play a lot of DotA for years (at some points for 12 hours a day), then quit cold turkey, then started again last year, but maybe 30-60 minutes a day.
After I started Mounjaro, I haven't really had the urge to play at all. I played a game a few weeks ago but I was kind of "meh" about it, and haven't played since. It's striking.
What does excite you instead now on the medication?
Making stuff, big time. I love making things with hardware, software, or 3D printing.
A few friends and I made a maker community, and over the weekend I made a semi-automated newsletter for links we post in our Discord (https://themakery.cc). I really had fun doing that, it was great.
Last few weekends, https://encyclopedai.stavros.io/, https://theboard.stavros.io/, https://pine.town/, and a few other bits and pieces.
I am generally a person that has a few beers each week. I haven't had a beer in a month since starting GLP-1. It just never sounded appealing.
Nah, obesity reduction is itself a downstream effect of messing with neurotransmitters. There have to be other consequences of that - both good and bad.
There don't have to be any other consequences, certainly not both good and bad ones. Biology doesn't actually have some scale of justice that means good things must be offset by bad things.
But yes, it's very probable (in fact we already know) the drug is doing several things in the body.
I was more thinking that evolved systems rarely have convenient switches you can flip and just get a single outcome. You perturb the system, and you get a cascade of changes. It's not like engineering.
Nothing about justice was implied, so lets say desirable and undesirable instead of good and bad.
Yes you’re right to be concerned about this, I’m taking issue with your assumption that there must be undesirable effects.
Makes sense, sadly.
Alzheimer's isn't one thing but a category of degenerative pathologies.
Probably also requires holistic improvements in lifestyle ( hydration, sleep, exercise, diet (not just quantity)), gene in/activation, &| vaccines for TAU &| β-amyloid.
PS: I wonder if nootropics will be developed to emulate or enhance the effects of exercise.
There is no way magic weight loss drug will have any unexpected downsides!
neither do most things in life