On GLP-1 agonists, you don’t get nearly the counterbalancing reduction in energy expenditure you usually see with caloric restriction. Your body keeps happily releasing lipid stores, assuming they will be replenished, but they aren’t. Hunger hormones remain untriggered, cortisol stays low, and insulin keeps shuttling glucose into cells to be burned.
If you aren’t metabolically deranged, your body does this anyway. But many people have totally decompensated metabolically due to excess energy intake over time, and essentially cannot recover without some kind of treatment.
GLP-1 is just the beginning — future compounds will do a better job maintaining muscle mass, for example. But this is looking like an absolute miracle, and once patent protection ends (especially for oral formulations), we’re going to be living in a very different world health-wise.
Modern medicine does have magic pills for many illnesses; for example, antibiotics are magical for many bacterial infections, many vaccines are almost magical too.
OTOH, many pills will have undesired side-effects, and the body is in a complex dynamic equilibrium, so it may happen that blocking GLP-1 may have side effects.
Eventually, we'll all die, but I'm optimistic that GLP-1 will lead to a better equilibrium. Preliminary evidence says it will. I'm not as confident as the author though :)
Always have been. Always will be.
You can achieve better effects than this poison simply by eating closer to how humans ate in the 1800's.
Are you sure there is such a thing?
How many average person years does an intervention need to save before it meets your approval?
Like I asked, where's our cutoff? If obesity on average kills you a couple of decades earlier than otherwise, does treatment for that meet your approval?
They're either the same or they're different.
> Like I asked, where's our cutoff?
Exigency of loss of life.
> kills you a couple of decades earlier
Staying obese into old age carries risks. There are multiple ways to manage that risk. None of it is as exigent as other conditions.
> does treatment for that meet your approval?
Universally? No.
> Exigency of loss of life.
Cool. How about cancer treatment? Some of those you can live with for some months/years. We allowed to treat anyway when the outcomes are better?
> Staying obese into old age carries risks. There are multiple ways to manage that risk. None of it is as exigent as other conditions.
And why should this not be one of the ways to manage that risk? The biggest difference seems to be that it actually works, on average, unlike some other common treatments like telling people to eat less and exercise more.
And that's mostly related to how much you move. If the body needs to reduce energy expenditure, there isn't much it can cut that's non essential that will make a difference, other than activity and movement in general. So you feel like laying on the couch all day.
I haven't tried GLP-1 myself, but reports seem to indicate that GLP-1 drugs make you feel _tired_, which is basically the same thing. So I am not sure the body is fooled that easily.
> many people have totally decompensated metabolically
Around 88% of americans have some level of metabolic dysfunction so that tracks. Numbers worldwide are trending up.
> and essentially cannot recover without some kind of treatment.
They can. Going back to a healthy food intake will fix anything that's not permanently damaged(and if it is permanently damaged, there isn't much medicine can do either). That can be sped up with other measures, such as fasting.
I am a bit skeptical of trying to fix a problem that was mostly created by the food industry with medication. GLP-1 isn't without side effects.
Cutting sugars and simple carbs in general has very similar effects and will decrease your hunger hormones as well. I think everybody should try that first before relying on medical interventions.
Besides, carbs tend to make you retain a lot of liquid. Drastically cutting them usually improves fluid retention, people see changes pretty quickly in the scale, and that can motivate them to continue. Do that long enough and even eating habits will change and so will your palate. A soda becomes unbearable.
I know a few people that take one of the name brands, and they really don't complain about this issue. What they do talk about is having more energy after dropping weight because they just don't feel compelled to eat much anymore.
I'm not overweight myself, but I am a Type 1 diabetic from a young age. "Sugar noise" is not something that is easy to ignore. Especially in the case where you have excess insulin in your bloodstream but not active enough for your body to use it. Your body will scream at you to eat something sweet/carby. In people that are overweight this can be caused by insulin resistance. Until you experience it, it's really easy to say "People should try", but it's about as easy as telling someone to drop meth or heroin.
My body SCREAMS for me to eat something sweet/carby all fucking day long. All day. Never realized the extent of it until using GLP-1s. I tried many things: full strict diets with macro counting, IF, more lenient and "natural-feeling" diets where you just try to eat whole foods that are filling and tasty. With or without weight lifting, sometimes cardio. Yeah they work, big surprise! But the entire time you are fighting against that urge, doesn't matter if you've gone a full month with perfect "discipline". Eventually it gets you. And I was miserable the entire time trying _not_ to think about food.
This is life changing.
Some people can do it but they're usually not among the huge percentage of obese people in the population.
With GLP-1 agonists it doesn't even feel like you're fighting your body because you just automatically don't want to eat too much (just like people who don't have problems managing their weight).
I think it's basically a good thing that modern day civilization has cheap and available calories because no one has to go hungry, but this is an environment that evolution just hasn't prepared us for and many many people are just not calibrated right for it. Maybe we can finally fix that.
I have been somewhat of a "casual bio hacker" for the past 25 years and have done things like quitting alcohol or caffeine cold turkey and staying off it for years, or tracking every calorie I ate for 10+ years. I've had periods of eating really healthy, I've had periods of eating whatever but staying in calorie deficit, I've had periods of just not eating much at all, I've had periods of eating anything and not caring. I've tried a variety of more extreme body modifications just to try it and note the results. I find messing with the body (or food intake or whatever) to be like trying to reverse engineer an unknown binary, or like trying to write a keygen but for your mood and health. It's been a little hobby of mine for a long time.
These medications are WAY different. There is no way to describe it. You just feel... better, in almost every way. As someone once posted on another thread, their relationship with food changed. I noticed my relationship with food changed as did my relationship with other minor vices; my "screen time" is down. My anxiety is almost entirely gone, my mood is better, and I feel like I sleep better.
Even as the weight loss rate decreased (which was dramatic at first but has mostly stopped as I didn't increase my dosage of the medications to see what would happen), I just feel... better.
No amount of eating better or healthy lifestyle that I've tried (and documented) in the past two decades has produced anything nearly as profound as the impact that Ozempic has, both on my mental and physical health. Which seems crazy, and I thought that people who were crowing about an off-label diabetes drug were crazy as you probably think I am. But I agree with these types of articles - GLP-1 drugs are just the first step in some kind of next step in health, and obviously right now the focus is on "lose weight, undo the damage of processed foods!" but I think we are going to find that GLP-1's are just the first of many new discoveries that could extend or improve our lives beyond the aesthetic reasons that people take them today.
Regarding side effects, I have a lot of people ask me or comment about this. I think just like any drug, you only hear about the people with bad side effects. 8% of American adults are taking a GLP-1 drug right now, yet CVS Pharmacy doesn't have a section dedicated to managing the side effects (but they do for opioid side effects like constipation), which would be my gauge as to how it's really going.
I did have some dehydration (far less than something like scopolamine gives me) on the first couple days after my first self injection, but increasing my water and electrolyte intake fixed that and it seems to have gone away (I've even tried lowering my water and electrolyte intake and it didn't come back). I am not more tired, nor do I have more (or fewer) digestive issues than before. I think people who do have increased digestive issues have just never experienced (or not recently) what happens when you are really full and just overeat, because their bodies are so used to higher calorie or sugar consumption. Just like how Thanksgiving dinner can make you tired or make you have to wait in the family line for the bathroom, I suspect that GLP-1's are causing some people's "normal" meals to feel to their body like a "Thanksgiving dinner" because they effectively are (by comparison). I have noticed some slight muscle loss in my non-dominant arm that is of mild concern but nothing that I am worried about at this time.
This is anecdotal yes and it's just my personal account of these medications but I was skeptical until I tried them, like you are, as I thought "oh, just eat healthy, why needs a shot".
I will update this post when it's determined that GLP-1's cause some crazy or horrible disease but for now I am enjoying this experiment with them.
Muscle loss large enough to be noticeable is concerning, and muscle loss is one of the side effects of these medications that has me most concerned. How did you notice that your off-arm is weaker?
What are you referring to here? The muscle-preserving medication? Are GLP-1s actively reducing your muscle mass, or is it the fact that people on them ate very little and didn't tend to exercise?
Making sure each meal contains substantial protein will help negate this.
I have one friend in particular who started a GLP-1 drug solely to assist in drinking less - she certainly does not need to lose any weight. It worked like a light switch for her and turned moderately problematic drinking into easily achieved light social drinking. No impact on appetite since she is on a very low dose.
I have had the same experience, even though I took it for weight loss to start with.
I do know that drinking can be downright unpleasant for me if I push through the aversion after my first drink and try to go for a few more. I have noticed a strong correlation to drinking and my blood sugar crashing rapidly afterwards while on Tirzepatide while wearing a glucose monitor.
A single cold beer on hot day with friends is still quite pleasant. Sitting in a bar for hours on end drinking heavily is simply downright uninteresting now before you get into any unpleasant side effects.
Is this based on your survey or her self assessment?
> Sitting in a bar for hours on end drinking heavily is simply downright uninteresting
Yet it used to be? You don't find this situation suspect?
Both? Being around her, and her self-assessment. Not sure how else one could interpret such a statement. This is all anecdotal evidence and should be taken as such.
> Yet it used to be? You don't find this situation suspect?
Yes, it used to be moderately interesting sometimes with the right people. Suspect in what manner? That it removes the desire to get inebriated? Perhaps so, since we do not understand the mechanism at play. What we don't know can certainly hurt us.
Overall the desire to drink less seems very similar to the impact it has on appetite and hunger levels. In that way, it is not so surprising to me.
For example we see the same behaviors in mice
https://www.niaaa.nih.gov/news-events/research-update/semagl...
>In the current study, the researchers demonstrated that semaglutide reduced binge-like alcohol drinking in both male and female mice, and that the effect was dose-dependent (i.e., greater amounts of semaglutide led to greater reductions in binge alcohol intake). The researchers also tested semaglutide in rats that were made dependent on alcohol through long-term exposure to alcohol vapor. They found that semaglutide reduced alcohol intake in this animal model, again with no sex differences.
It is not documented, so no, it is not. Which is why I questioned if it was entirely based on self assessment or not and left the door open either way as the question was based out of curiosity and if his anecdote was public I wanted the answer to be as well. Is that not fair?
> when those pieces of data come together it provides evidence.
When you properly document them it literally stops being an anecdote and then becomes evidence.
> The researchers also tested semaglutide in rats that were made dependent on alcohol through long-term exposure to alcohol vapor.
So.. what are we actually measuring then? Isn't alcoholism a disease and not some acquired exposure based dependency? The idea that "GLP-1 for Everything" is even floated in this way is unusual in and of itself. I'm uncomfortable with all this and am once again annoyed at the way we use rats in research.
https://jamanetwork.com/journals/jamaneurology/fullarticle/7... https://www.pnas.org/doi/10.1073/pnas.0808587106
> Conclusion: Higher intake of calories and fats may be associated with higher risk of [Alzheimer Disease] in individuals carrying the apolipoprotein E ϵ4 allele.
> The hazard ratios of [Alzheimer Disease] for the highest quartiles of calorie and fat intake compared with the lowest quartiles in individuals without the apolipoprotein E ϵ4 allele were close to 1 and were not statistically significant.
For the general population, there was no correlation. Identifying specific genetic outliers where there may be a connection is still useful, but far from a general result.
The real surprise I learned is that GLP-1 may discourage other addictions as well, including gambling. Source: A nurse I talked to who works with GLP-1 trials.
There is also a huge correlation between obesity and type 2 diabetes as well.
I imagine they share similarities, but that’s pure speculation.
Human metabolism is sensitive to the type of food you eat.
Check https://www.metabolicmind.org/ as a starting point and follow the rabbit hole to understand the link between what you eat and mental and metabolic illness.
Also, GLP-1 also eliminates muscle - your heart is a muscle.
When you are losing 5% of your bodyweight per month (as I was, and many do) a substantial portion of that is simply going to be mean muscle mass. You can counteract some, but not all, of this by heavy resistance training. It's very difficult to not lose muscle mass while losing weight - it takes extreme measures for most folks (e.g. athletes) to do so.
No it's not.
https://pmc.ncbi.nlm.nih.gov/articles/PMC2769828/#:~:text=We....
You can't get people in large enough quantities to do that reliably and for long enough as part of a study. Best you can do is a small quantity of lab rats.
The data is already rolling in as part of prescribed out-patient data.
It's really interesting to me that there's some evidence for Metformin -- a diabetes drug that suppresses glucose production and appears to do other things we don't fully understand -- having general health benefits and possible life extending benefits in healthy people. Normally it's just used to treat some forms of diabetes.
Feels like we're on the cusp of figuring something out about inflammation, aging, and metabolism.
veg fats okay, animal fats no so much as if you limit them you tend to live longer due to the decrease in oxidative damage.
Societies consuming high amounts of oxidized oils (repeatedly heated cooking oils, whether plant or animal) show increased rates of cardiovascular disease
Mediterranean populations consuming fresh, minimally processed olive oil show better cardiovascular outcomes
Populations with high fresh fish consumption (like traditional Japanese diets) show better health outcomes despite high PUFA intake, likely due to immediate consumption and minimal oxidation
Modern food processing/storage methods increase exposure to oxidized fats
Fast food consumption correlates with higher intake of oxidized fats due to repeated oil heating
Socioeconomic factors influence exposure - processed foods with oxidized fats are often cheaper and more accessible
Oxidation status of fats may be as important as the traditional saturated/unsaturated classification
Can you elaborate on that? Aren't animal fats, particularly dairy, rather rich in saturated fats? And saturated fats oxidize less easily than unsaturated fats precisely because they lack weak double bonds.
It might be awhile before the research propagates to the realm of popular science.
IMO, it kind of represents how incredibly blind we are to supposedly safe compounds, and how arrogant others are for calling for less regulation. When attention is high, suddenly so much more is revealed.