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Re:GLP-1 for Everything by didgeoridoo on Tuesday October 29, 2024 @03:43PM (#41988524)
Eating less food and keeping your body from knowing it seems to be a big part of why it works.

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.

Re:GLP-1 for Everything by arijo on Tuesday October 29, 2024 @03:55PM (#41988622)
Assuming you're going to fix a extremely complex system like the human body by just taking a pill is what some people call the bias of Illusion of Control.

https://en.wikipedia.org/wiki/Illusion_of_control

Re:GLP-1 for Everything by didgeoridoo on Tuesday October 29, 2024 @04:00PM (#41988667)
You’re going to have to be more specific, because I am sure you are not arguing against the concept of medicine.
Re:GLP-1 for Everything by arijo on Tuesday October 29, 2024 @04:06PM (#41988741)
I argue that medicine still does not have enough accumulated knowledge about the complexity of the human body to be playing God with a single pill.
Re:GLP-1 for Everything by kelseyfrog on Tuesday October 29, 2024 @04:19PM (#41988891)
You may begin your argument now
Re:GLP-1 for Everything by cyberax on Tuesday October 29, 2024 @04:22PM (#41988935)
There is no god. So I argue that medicine is at least just as potent as nothing.
Re:GLP-1 for Everything by okaram on Tuesday October 29, 2024 @04:29PM (#41989011)
Maybe ... maybe not.

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 :)

Re:GLP-1 for Everything by emptiestplace on Tuesday October 29, 2024 @04:31PM (#41989030)
You're right, but the way you're going about it isn't.
Re:GLP-1 for Everything by kadoban on Tuesday October 29, 2024 @04:32PM (#41989039)
Any single pill? Or is your objection specific to this one? (That iirc is actually an injection, not a pill, but w/e)
Re:GLP-1 for Everything by herval on Tuesday October 29, 2024 @04:36PM (#41989078)
You don’t believe the medicine that billions of people take to treat diseases that would’ve otherwise demonstrably killed them is “accumulated knowledge” enough? From insulin to antibiotics, we have sufficient evidence that many types of medicine DO work. Nobody is “playing god” (whatever that means), it’s just reproducible and consistent data
Re:GLP-1 for Everything by breck on Tuesday October 29, 2024 @04:04PM (#41988722)
Patented medicines aren't medicine, they're poisons.

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.

[0] https://breckyunits.com/patentsArePoison.html

Re:GLP-1 for Everything by malfist on Tuesday October 29, 2024 @04:24PM (#41988949)
Try telling a type 1 diabetic patient to eat like it's the 1800s
Re:GLP-1 for Everything by breck on Tuesday October 29, 2024 @07:59PM (#41990709)
> a type 1 diabetic patient

Are you sure there is such a thing?

Re:GLP-1 for Everything by malfist on Wednesday October 30, 2024 @10:09AM (#41995004)
Yes.
Re:GLP-1 for Everything by breck on Wednesday October 30, 2024 @03:08PM (#41998995)
And what biological test can one conduct that proves this, and is unchangeable over time?
Re:GLP-1 for Everything by kadoban on Tuesday October 29, 2024 @04:30PM (#41989024)
Are diabetics biased in this way when they take insulin? Or where is your cutoff?

How many average person years does an intervention need to save before it meets your approval?

Re:GLP-1 for Everything by akira2501 on Tuesday October 29, 2024 @04:35PM (#41989074)
Untreated diabetics can die within a week. Are we facing the same sort of problem here?
Re:GLP-1 for Everything by kadoban on Tuesday October 29, 2024 @04:39PM (#41989122)
No, but same thing with different numbers.

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?

Re:GLP-1 for Everything by akira2501 on Tuesday October 29, 2024 @04:53PM (#41989284)
> No, but same thing

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.

Re:GLP-1 for Everything by kadoban on Tuesday October 29, 2024 @05:01PM (#41989362)
>> Like I asked, where's our cutoff?

> 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.

Re:GLP-1 for Everything by scheme271 on Tuesday October 29, 2024 @04:43PM (#41989156)
Patent protection for the early versions has already ended. Teva is making generic versions of liraglutide and it's been available in the US for a few months. The other GLP-1 agonists will be protected for a few more years though.
Re:GLP-1 for Everything by didgeoridoo on Tuesday October 29, 2024 @06:34PM (#41990108)
True but imagine the price and availability impact when the oral formulations go off-patent. The autoinjectors are inherently expensive to make and ship, and some people have a needle phobia. Oral daily seems like the endgame here.
Re:GLP-1 for Everything by outworlder on Tuesday October 29, 2024 @05:17PM (#41989491)
> On GLP-1 agonists, you don’t get nearly the counterbalancing reduction in energy expenditure you usually see with caloric restriction

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.

Re:GLP-1 for Everything by pixl97 on Tuesday October 29, 2024 @05:49PM (#41989763)
>but reports seem to indicate that GLP-1 drugs make you feel _tired_,

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.

Re:GLP-1 for Everything by babyoil on Tuesday October 29, 2024 @06:09PM (#41989933)
I am overweight. That food and sugar noise thing is real and brutal. Your parent comment should really factor that in the discussion. I know it's hard because (fortunately) they may not have experienced this themselves, but it's horrible.

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.

Re:GLP-1 for Everything by chpatrick on Tuesday October 29, 2024 @06:13PM (#41989973)
As public health policy though, just telling people to do the things you describe doesn't work because dieting sucks and your body doesn't want you to do it.

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.

Re:GLP-1 for Everything by jasongill on Tuesday October 29, 2024 @06:02PM (#41989882)
I've been taking Ozempic or Zepbound for a couple months as a personal experiment and the effects have been nothing short of life-changing.

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.

Re:GLP-1 for Everything by adiabatty on Thursday October 31, 2024 @12:50AM (#42003606)
> 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.

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?

Re:GLP-1 for Everything by jasongill on Thursday October 31, 2024 @09:52AM (#42006921)
I haven't measured in a while and I don't feel "weak" per se, but I did notice in the mirror that my left bicep seems to be smaller than I remembered (and that's an area that I don't really have any fat buildup which might just be disappearing due to weight or water loss). I also haven't been doing any workouts (intentionally, just to see what happens on GLP-1 meds) but I suspect just some simple workouts would help. For me right now, after ~4mo it's not enough to concern me more than just "ah, guess I should find the weights some time" but I am keeping an eye on it. Otherwise I haven't noticed anything else so it may not be related or might just be me being paranoid
Re:GLP-1 for Everything by stavros on Tuesday October 29, 2024 @05:21PM (#41989533)
> But this is looking like an absolute miracle

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?

Re:GLP-1 for Everything by schnebbau on Tuesday October 29, 2024 @05:53PM (#41989805)
Losing muscle mass is just what happens when you're in a calorie deficit. The same thing happens if you're in a calorie deficit without the aid of a GLP-1.

Making sure each meal contains substantial protein will help negate this.

Re:GLP-1 for Everything by didgeoridoo on Tuesday October 29, 2024 @06:31PM (#41990096)
Right, it’s not something specific to GLP-1 treatment, but there are myostatin and activin A modulators under investigation to specifically counteract muscle loss related to caloric deficit more generally.