[HN Gopher] GLP-1 for Everything
___________________________________________________________________
GLP-1 for Everything
Author : etiam
Score : 124 points
Date : 2024-10-29 19:15 UTC (3 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| mentos wrote:
| Isn't this just eating less food is good for everything?
| api wrote:
| Do we know? I think that's the question being asked here. Using
| these drugs seems to improve a bunch of indicators and we're
| not sure why.
|
| 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.
| breck wrote:
| Yes. Turns out everyone should have just been eating fats all
| along.
| fredgrott wrote:
| hmm, ahem no!
|
| 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.
| greenavocado wrote:
| Polyunsaturated fatty acids (PUFAs), whether from plants or
| animals, are most susceptible to oxidative damage because
| they have multiple double bonds that can react with oxygen.
| Each double bond creates a potential site for oxidation.
|
| 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
| david-gpu wrote:
| _> if you limit them you tend to live longer due to the
| decrease in oxidative damage_
|
| 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.
| Etheryte wrote:
| There is no known link between how much you eat and Alzheimers,
| substance abuse, etc. If it was as simple as eating less makes
| these issues go away, we would've figured that out a long long
| time ago.
| dmicah wrote:
| There have previously been associations between caloric
| intake and Alzheimer Disease or Cognitive Aging, for example:
|
| https://jamanetwork.com/journals/jamaneurology/fullarticle/7.
| .. https://www.pnas.org/doi/10.1073/pnas.0808587106
| Etheryte wrote:
| I think it's a fair bit of a stretch to broadly say that
| this study shows an association.
|
| > Conclusion: Higher intake of calories and fats may be
| associated with higher risk of [Alzheimer Disease] in
| individuals carrying the apolipoprotein E [?]4 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 [?]4 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.
| arijo wrote:
| Alzheimer's is now being referred as type 3 diabetes for a
| reason.
|
| 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.
| phil21 wrote:
| GLP-1 reduces calorie intake and puts many people on a
| deficit (typically on purpose). This of course will reduce
| muscle just like any other calorie deficit anyone runs long
| term.
| johnyzee wrote:
| Fasting increases growth hormone release (dramatically,
| in the case of extended fasting), which counters muscle
| loss. Does this happen with GLP-1?
| phil21 wrote:
| This goes against all evidence I have seen for folks who
| have lost a drastic amount of weight very rapidly.
| Bodybuilders seem to see the same effect as well when on
| cuts.
|
| 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.
| cyberax wrote:
| > Alzheimer's is now being referred as type 3 diabetes for
| a reason.
|
| No it's not.
| ZYbCRq22HbJ2y7 wrote:
| Some are referring to it that way
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC2769828/#:~:text
| =We....
| Etheryte wrote:
| What you eat is a very different concept to the amount you
| eat. Especially on topics like these, the distinction is
| critical.
| bb88 wrote:
| Exactly. There are lots of skinny alcoholics and drug
| addicts. Unfortunately many of them are homeless.
|
| 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.
| phil21 wrote:
| As others have already stated, it's starting to become
| mainstream science that there is a strong correlation between
| obesity/poor body composition and Alzheimers. It's not
| settled science yet, but the correlation is starting to look
| a whole lot like causation at a society level.
| eli_gottlieb wrote:
| Not to cite anecdotal evidence, but my father-in-law was
| skinny as a rail and got severe, early-onset Alzheimer's.
| Obesity might be one potential cause of Alzheimer's, but
| it's among many.
| phil21 wrote:
| Yep, just like there are skinny as rails type 2
| diabetics. My grandfather was one.
|
| There is also a huge correlation between obesity and type
| 2 diabetes as well.
|
| I imagine they share similarities, but that's pure
| speculation.
| ugh123 wrote:
| >If it was as simple as eating less makes these issues go
| away, we would've figured that out a long long time ago.
|
| 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.
| slaymaker1907 wrote:
| Depends on who you are and if you have an eating disorder.
| didgeoridoo wrote:
| 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.
| arijo wrote:
| 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
| didgeoridoo wrote:
| You're going to have to be more specific, because I am sure
| you are not arguing against the concept of _medicine_.
| arijo wrote:
| 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.
| kelseyfrog wrote:
| You may begin your argument now
| cyberax wrote:
| There is no god. So I argue that medicine is at least
| just as potent as nothing.
| okaram wrote:
| 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
| :)
| emptiestplace wrote:
| You're right, but the way you're going about it isn't.
| kadoban wrote:
| Any single pill? Or is your objection specific to this
| one? (That iirc is actually an injection, not a pill, but
| w/e)
| herval wrote:
| 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
| kadoban wrote:
| 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?
| akira2501 wrote:
| Untreated diabetics can die within a week. Are we facing
| the same sort of problem here?
| kadoban wrote:
| 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?
| akira2501 wrote:
| > 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.
| kadoban wrote:
| >> 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.
| scheme271 wrote:
| 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.
| didgeoridoo wrote:
| 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.
| outworlder wrote:
| > 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.
| pixl97 wrote:
| >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.
| babyoil wrote:
| 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.
| jasongill wrote:
| 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.
| chpatrick wrote:
| 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.
| stavros wrote:
| > 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?
| schnebbau wrote:
| 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.
| didgeoridoo wrote:
| 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.
| david-gpu wrote:
| Does eating less food reduce addiction to tobacco, alcohol and
| other substances? Because there is mounting (but not
| conclusive) evidence that GLP-1 agonists do just that.
| phil21 wrote:
| Sample of only a half dozen people close enough to me to talk
| intimately about it - but for drinking it's been absolutely
| proven in my mind for some people.
|
| 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.
| herval wrote:
| Add me to that sample set, I drink far, far less with it
| akira2501 wrote:
| > turned moderately problematic drinking into easily
| achieved light social drinking.
|
| 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?
| phil21 wrote:
| > Is this based on your survey or her self assessment?
|
| 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.
| pixl97 wrote:
| FFS. An anecdote is one piece of data, when those pieces
| of data come together it provides evidence.
|
| 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.
| Jhsto wrote:
| I wonder if it's about more stable glucose levels hence
| avoidance of cravings. Anecdotally, alcohol and nicotine
| cravings seem to pass me whenever I have a particularly fast
| acting (low osmolality) carbohydrate supplement.
| loeg wrote:
| I don't think we know conclusively yet. That probably explains
| quite a lot of it, yes. It's unclear how that would lead to the
| substance (ab)use results, though.
| erulabs wrote:
| Born too late to die in infancy, born too early to see
| immortality.
|
| I imagine parents in the 1890s felt the same way. Our children
| will see a new and different world than we can imagine. I love
| this topic of moving past "health" and towards something better.
| To quote an 1890s thinker: "it's time to find out what value our
| values really had".
|
| This does remind me of the superconductor stuff tho - I'm too
| excited - it will be interesting to see what focused clinical
| studies show us here, particularly around GLP-1's effects on
| addiction.
| modeless wrote:
| The most important question in the world right now is: which
| generation will be the first to live indefinitely? It is clear
| to me that we are on a trajectory to achieve indefinite
| lifespan extension, but unlike Kurzweil et al I don't see a
| real possibility that it will happen soon enough for me
| personally. Maybe my kids, or maybe one or two generations
| further.
|
| Will it happen soon enough to prevent population collapse due
| to plummeting fertility rates? Will fertility rates go even
| lower or will the population start to rise again as deaths
| fall? Will we see stagnation due to older brains being stuck in
| their ways, or will we be able to fix that too?
| andrewmcwatters wrote:
| Born just in time to live too long and outlive your savings
| while modern monetary policy infinitely reduces the value of
| your local currency!
| bartwr wrote:
| It's interestingly disingenuous that many claim of GLP-1 agonist
| miraculous effects on all kinds of health problems, where the
| same problems are "simply" solved by getting on a calorie deficit
| and lean. Liver, kidneys, heart, etc. If you have a non-alcoholic
| fatty liver disease and are obese, getting leaner will heal it.
| All those impressive results are on obese or diabetic people. So
| it is not only not a surprise, but also dishonest marketing or
| ignorance.
|
| Don't get me wrong - those are miraculous drugs. First real non-
| stimulant low side effect appetite suppresion that will help
| millions. But let's wait for honest research on _lean_ people
| before spreading marketing on how it improves overall health.
|
| Also, how nobody mentions the need for increasing the dosage and
| tolerance build-up (just check reddits how much people end up
| having to take after months of continuous use). You cannot be on
| it "for life".
| majormajor wrote:
| I don't know that you have to be disingenuous to both be
| enthused about these medications AND wish we'd never created
| the super-processed, super-sugary, make-people-crave-them-and-
| overeat-them modern American diet. Once you fuck with your gut
| biome for long enough it's not "simple" to solve it. It's
| incredibly difficult both discipline and metabolism-wise.
| bbatha wrote:
| The increasing dosage is to tritrate up to a dose not because
| you gain tolerance. There are patients on GLP-1 for over a
| decade. Also maintenance and weight loss dosages are different:
| see the dosing charts for ozembic vs wegovy which are exactly
| the same drug.
|
| Even if folks gain tolerance that doesn't seem overly
| concerning. Mental health drugs also have tolerance issues and
| changing medicines every few years, while it has challenges for
| the patient, is an accepted part of long term psychiatric
| treatment.
| leetnewb wrote:
| Just a narrow comment, but type 2 diabetes certainly isn't
| limited to the obese. Many lean people develop issues with
| blood sugar that can't be controlled with diet alone.
| bearjaws wrote:
| A friend's son, who is an EMT, was recently diagnosed with
| type 2 diabetes at the age of 21. He doesn't drink or eat
| sweets, except on holidays, and works out five days a week.
| Suddenly, he started feeling sick, was vomiting, and ended up
| in the ER, all within three days. It can really hit you like
| a truck.
| corry wrote:
| This is my #1 question on GLP-1: are we just seeing how humans
| do much, much better by being lean vs. the direct result of the
| drug?
|
| A lean current-epoch human -- with our food abundance, access
| to modern medicines, higher standards of life, lower risks of
| injury, etc -- is likely going to be markedly healthier than a
| non-lean current-epoch human or a lean human from a prior age
| where medicine/food/etc was worse.
|
| Or is it, in fact, the direct result of the drug?
| pdabbadabba wrote:
| > where the same problems are "simply" solved by getting on a
| calorie deficit and lean
|
| Except that there apparently is mounting evidence that GLP-1
| agonists also address some issues that are not generally
| addressed by just restricting calories. TFA touches on this
| briefly: "The weight loss involved with GLP-1 agonist treatment
| is surely a big player in many of these beneficial effects, but
| there seem to be some pleiotropic ones beyond what one could
| explain by weight loss alone."
|
| I seem to recall seeing claims that they reduce COVID-19
| mortality even controlling for BMI (possibly because they
| inhibit systemic inflammation), reduce alcohol consumption, and
| even (though I think just anecdotally) may help overcome
| gambling addiction.
|
| See, for example:
|
| https://pmc.ncbi.nlm.nih.gov/articles/PMC8425441/ [COVID-19]
|
| https://www.ncbi.nlm.nih.gov/search/research-news/19361/
| [Addiction]
| levocardia wrote:
| Color me a bit skeptical on the "GLP-1 is the cure for
| everything" hype. These drugs are clearly a game-changer for
| obesity and T2D, and possibly a few other conditions, but it
| strikes me as unlikely that a chemical exists that is more or
| less an across-the-board improvement to health, with no
| downsides. If it was that simple, why didn't the human body just
| evolve to excrete GLP-1 agonists? Or modify GLP-1 itself?
|
| The best argument against is "starvation was a human universal"
| and that survival through famines totally dominated the
| evolutionary trend in GLP-1 related things in the body. But even
| something as simple as lactose tolerance responded quite quickly
| to changes in human dietary structure in different areas of the
| world.
|
| My suspicion is that at least some of these medical record review
| studies are just driven by confounding - people who find out
| about GLP-1 agonists are better educated, wealthier, or have
| behavioral/lifestyle traits that explain many of the apparent
| benefits.
|
| (still, part of me is still holding out for the "miracle drug"
| explanation)
| majormajor wrote:
| > If it was that simple, why didn't the human body just evolve
| to excrete GLP-1 agonists?
|
| Because we haven't had the infinite years required to "just
| evolve" every possible bodily improvement?
|
| I don't know if it's an ideal wonder drug or also has downsides
| we haven't found yet or some of the positives are
| misinterpreted but if "why didn't we just evolve it" was
| meaningful it could be an argument against ANYTHING being good
| in the way presented.
| manmal wrote:
| To be fair, we don't need infinite years/generations to
| select for favorable traits.
|
| Such a selection process might already be underway - obesity
| lowers fertility, so there is pressure towards not being
| obese. IMO the next generation will already be either
| slightly reducing their intake, or increase their expenditure
| of calories. There's many ways to do that - becoming taller,
| more restless, less hungry, decreasing intestinal uptake,
| reduced enjoyment of food (loss of taste/smell) etc
| pixl97 wrote:
| Fertility is one of those things that's dropped faster than
| obesity has increased in most places and will have a much
| greater impact on future generations.
| thierrydamiba wrote:
| Is it addictive at all?
| SomeHacker44 wrote:
| In the sense that you need a constantly increasing amount to
| maintain the same results: yes.
| hcazz wrote:
| That's incorrect. It's a titrated drug similar to blood
| pressure meds. If you have effectiveness at a 1mg dose for
| example, you stay at that. The drugs have maximum doses.
| chrisoconnell wrote:
| I think it's important to call out that it's actually
| constantly increasing amount to increase the results.
|
| As patients lose weight, they need to eat fewer and fewer
| calories to continue to lose weight, as the BMR decreases.
| This isn't because of the medication, but rather because it
| requires fewer calories to maintain their mass, so they
| burn fewer calories at rest.
|
| Increasing the dose further decreases hunger signals, which
| further decreases their desire to eat as much.
|
| It's not "increasing to maintain the same results" its
| "increasing to increase results".
|
| Ex.
|
| Patient A currently weighs 330lbs. Has a BMR of 3300
| Calories. - Initial dose, they eat 2,800 calories a day
| instead of 3,500 calories they used to. - Loses weight. Now
| weighs 250lbs. - BMR is roughly now weighs 250lbs, and has
| a BMR of roughly 2500 calories, but dose still has them
| eating around 2,800 calories. - Dose is increased, patient
| is now eating around 2,000 calories. - Patient A reaches
| 200lbs, BMR is roughly 1,800 calories, but is still eating
| 2,000 calories. - Dose is increased, Patient A is now
| eating 1600 calories.
| ben_w wrote:
| > If it was that simple, why didn't the human body just evolve
| to excrete GLP-1 agonists? Or modify GLP-1 itself?
|
| Because evolutionary fitness doesn't care about what we care
| about, and even if it did it operates so slowly it hasn't yet
| finished adapting to us having invented cooking.
|
| That said, I share your skepticism. This kind of story feels
| almost exactly like the old Victorian (literal) snake oil
| advertising:
| https://commons.m.wikimedia.org/wiki/File:Clark_Stanley%27s_...
| corry wrote:
| True, but (a) maybe it would evolve "naturally" given enough
| time, and (b) the things that humans create are a product of
| evolution too, no? Albeit not directly through the mechanism
| of natural selection.
| kaibee wrote:
| > True, but (a) maybe it would evolve "naturally" given
| enough time,
|
| You could say the same for myopia. But we still make
| glasses for people, which breaks the natural selection
| process that would drive that evolution.
| eli_gottlieb wrote:
| >If it was that simple, why didn't the human body just evolve
| to excrete GLP-1 agonists? Or modify GLP-1 itself?
|
| Honestly? I'm not much of a physiologist, but based on the
| effects regarding addictions like tobacco or narcotics that
| _cannot_ be causally downstream _just_ of diet, I 'd wonder if
| GLP-1 agonists aren't actually impacting stress-interoception
| systems rather than just hunger and metabolism. Under that
| hypothesis, the evolutionary reason would be: because we
| evolved to undergo stress mostly in physically strenuous,
| energy-burning situations, while high loads of cognitive and
| emotional stress _without_ physical effort are a novelty to
| post-industrial lifestyles.
| jstanley wrote:
| > If it was that simple, why didn't the human body just evolve
| to excrete GLP-1 agonists? Or modify GLP-1 itself?
|
| Replace "GLP-1" with any of: aircraft, computers, buildings,
| WiFi, ...
|
| Some things are easy for nature to find and some things aren't!
|
| And even of the things that are easy for nature to _find_ , and
| that we would have found useful even in the environment of
| evolutionary adaptation, they might not confer overall fitness
| if they are too costly.
| criddell wrote:
| Well said. Diseases that affect the elderly don't get a lot
| of consideration from nature. Natural selection really only
| cares about us reproducing.
|
| On top of all that, our current environment and diet are
| quite a bit different from the norm over the past few million
| years.
| TechDebtDevin wrote:
| Go to the glp-1 related Subreddits and you'll see they aren't
| all wealthy educated people. Hell I read a story of a girl on
| the Manjaro subreddit who couldn't get her meds and ate herself
| into the ER in two days.
|
| My sister takes Ozempic and is the proto-typical obese white
| girl with way too many kids she can't afford and only eats
| trash. It probably saved her life.
| jvanderbot wrote:
| Why didn't evolution make us smart enough to not overeat?
| herval wrote:
| There's no evolutionary benefit to eating as little as
| possible any time in human history, other than the past few
| decades. We're barely into the third generation where calory
| overconsumption is an issue. It takes a few hundreds of
| thousands more to evolve something this complex, with a
| population as global as ours
| nkozyra wrote:
| > There's no evolutionary benefit to eating as little as
| possible any time in human history
|
| In multiple organisms we see that under-eating and fasting
| extends lifespan, so I'm not sure that's the case.
|
| https://www.nature.com/articles/s41392-022-01163-z
|
| https://www.science.org/content/article/why-eating-less-
| mean...
|
| https://www.nature.com/articles/d41586-024-03277-6
| herval wrote:
| Humans (and other mammals) starve to death way more often
| than died of calorie overconsumption, since the first
| little mammal climbed a tree
| nkozyra wrote:
| Eating at little as possible means enough to live,
| though. That's what the "as possible" means, otherwise it
| would be "not eating"
| scheme271 wrote:
| Yeah but lifespan benefits usually come after the animal
| has had a lot of chances to have offspring. Also
| undereating is much more likely to kill you in times of
| famine.
| jvanderbot wrote:
| This was a rhetorical question.
| dleary wrote:
| The obesity epidemic is only 50 years old. GLP-1 seems to be a
| "thing that fixes your satiety balance", that is applying to
| more than just food, but maybe also help you regulate yourself
| when you have way too much access to alcohol, drugs, etc.
|
| In short: the reason that the human body wouldn't have evolved
| to make more GLP-1 automatically yet is because evolution
| causes _populations of organisms_ (not individuals) to change,
| over generations, to be better suited to their environment.
|
| And 50-100 years is nothing in terms of evolution. We spent
| 500k years evolving to optimize gathering every calorie we can.
| And then yesterday it turned out that maybe it is in fact
| possible to have too much.
|
| Also, the human body _does_ make some GLP-1 itself. Maybe it
| was just getting started.
| rictic wrote:
| I'm putting increasing probability on the idea that there's
| something in our modern environment that's disrupting the GLP-1
| metabolism (or a related system), these drugs are counteracting
| that effect.
|
| When it was just appetite suppression, that made sense, we're
| not adapted to a modern degree of plenty. Not sure that
| explains the other positive effects, if these results
| reproduce.
| nick__m wrote:
| My bet is on the HFCS in the processed food.
| pixl97 wrote:
| Look at all countries that are having rapid increases in
| obesity and see how many use HFCS to see if you're on the
| right track.
| modeless wrote:
| > If it was that simple, why didn't the human body just evolve
|
| That's easy to answer. We exist today in a _very_ different
| environment to that we evolved in.
|
| It makes perfect sense that there could be a hormone that
| wouldn't provide a net reproductive benefit to hunter-gatherers
| or subsistence farmers but provides an immense health benefit
| to sedentary humans eating unlimited food. In fact, it would be
| surprising if there _wasn 't_.
| zosima wrote:
| GLP-1 of course is the GLP-1 agonist created by the body.
|
| I don't think that humans eat to obesity by default. People
| have had adequate food for quite long and not grown fat.
|
| Maybe there is something in out environment or our foods that
| are blocking the GLP-1 receptor? If a modern food company
| discovered something like that they'd immediately realize that
| (unintentionally) they sell better, probably without realizing
| what they had created.
| matthewdgreen wrote:
| A good amount of GLP-1 is made in the intestines, and
| production is heavily affected by interactions between those
| cells and gut bacteria. So anything that caused dysbiosis of
| the gut microbiome could potentially be causing problems with
| natural GLP-1 emissions, e.g., antibiotics in the food
| supply, emulsifiers, etc.
| eropple wrote:
| _> People have had adequate food for quite long and not grown
| fat._
|
| That's revisionist, both in terms of "for quite long" (food
| insecurity was common _in America_ until about World War II,
| and massive food surplus available at consumer-cheap prices
| begins a little later; other countries still suffer from food
| insecurity today) and that people haven 't grown fat when
| able to do so. Being wealthy enough to the point of being
| _able_ to be fat has been A Thing for a thousand years. We
| know this because the medieval Catholic Church felt that they
| had to preach moderation; if they had to preach it, it 's
| because it wasn't happening as a universality.
| drowsspa wrote:
| Not really. Being fat was a sign of being rich back then,
| because only rich people could even have enough surplus
| calories to get fat.
| timr wrote:
| > My suspicion is that at least some of these medical record
| review studies are just driven by confounding - people who find
| out about GLP-1 agonists are better educated, wealthier, or
| have behavioral/lifestyle traits that explain many of the
| apparent benefits.
|
| This exactly. There was a recent paper about Ozempic and (IIRC)
| dementia that saw that the drug acted implausibly quickly to
| prevent illness -- the Kaplan Meier curves were literally
| separated at day 0. [1]
|
| Confounding is rampant in this area. The people who published
| the paper I linked below should not be scientists. It's
| embarrassing. Anyone who cites it in support of Ozempec as a
| miracle drug has revealed that they don't know what they're
| doing, and should be ignored, with prejudice [2].
|
| More generally, it's depressing that so many people are piling
| on here to tell you that you're wrong, based on little more
| than their "knowledge" that obesity is bad. The fact is that
| most of the science around GLP-1 agnoists and anything other
| than obesity is weak, to say the least.
|
| [1] I believe it was this paper. Certainly, the KM curves in
| this are ridiculous: https://alz-
| journals.onlinelibrary.wiley.com/doi/10.1002/alz...
|
| [2] Sadly, this appears to include the "Alzheimer's
| Association"...though you sort of understand why they're biased
| in favor of miracles.
|
| EDIT: I am just now realizing that Derek Lowe is citing this
| paper. Oy vey.
| MarkusQ wrote:
| Those graphs are incredible. Literally. As in impossible to
| credit.
|
| What sort of other things would we have to conclude if we
| took them seriously? Insulin causes AD, starting the day you
| get the prescription? The mind (assuming it's turned on and
| operating) boggles.
| timr wrote:
| One of the disappointing things in my life has been the
| discovery of how much "medical science" is based on
| statistical illiteracy.
| danielmarkbruce wrote:
| drop the "medical", it's cleaner.
| manmal wrote:
| The lactose adaption took a couple thousand years to develop,
| no? While the last famines in developed countries took place
| less than 100 years ago. Feeling less hungry does feel like an
| elegant solution to the blatant oversupply humans are facing
| now.
| hbosch wrote:
| >an across-the-board improvement to health
|
| Obesity is itself an across-the-board impairment to health.
| Anything with a positive impact on obesity will be, therefore,
| an across-the-board improvement to health.
| cschmidt wrote:
| This exact line of reasoning is the cover story on the Economist
| this week:
|
| Briefing:
| https://www.economist.com/briefing/2024/10/24/glp-1s-like-oz...
|
| Leader (opinion piece):
| https://www.economist.com/leaders/2024/10/24/its-not-just-ob...
|
| (sorry, paywalled)
| toomuchtodo wrote:
| https://archive.today/D06ZN
|
| https://archive.today/YgiWx
| RachelF wrote:
| This can also be viewed as advertising - there are board
| members in common between The Economist's holding company and
| Novo N.
| jpadkins wrote:
| I haven't seen any comments on the topic of chronic inflammation.
| I am not knowledgeable on this topic, but we do know that chronic
| inflammation is linked to a huge number of disease end points.
| GLP-1 may be reducing (or preventing) systemic inflammation.
|
| https://en.wikipedia.org/wiki/Systemic_inflammation
| kelseyfrog wrote:
| The main difference between GLP-1 agonists and telling people to
| eat less/better is that one works and one doesn't.
| akira2501 wrote:
| Obesity rates are not consistent across the world or time.
| Neither work. They just hide symptoms of the larger problem.
| toomuchtodo wrote:
| The problem is the human existing in a modern environment
| that is hostile to it. GLP-1s enable the human to more
| effectively operate in said environment. It patches
| malfunctioning reward centers (addiction and food
| compulsion), it reduces overall inflammation, it provide
| cardiovascular protective properties.
|
| As kubectl_h mentions [1], the future is better understanding
| and fine tuning the mechanisms responsible. I think gene
| therapy is the end goal (permanent fix vs chronic maintenance
| with GLP-1s), but others have indicated in previous threads
| that might not be possible. We need more information and
| research. This is only the beginning of the "Aha!" moment
| (The most exciting phrase to hear in science, the one that
| heralds new discoveries, is not "Eureka" but "That's
| funny..." --Isaac Asimov).
|
| [1] https://news.ycombinator.com/item?id=41989101
| akira2501 wrote:
| > in a modern environment that is hostile to it.
|
| Our ancient environment was hostile as well.
|
| > It patches malfunctioning reward centers
|
| It has an impact on them. It does not "patch" them. This is
| not a rational way to describe any drug.
|
| > it reduces overall inflammation
|
| It can inhibit certain inflammatory pathways.
|
| > it provide cardiovascular protective properties.
|
| It reduces the number of cardiovascular events. Whether
| that number is normal to begin with is not considered here.
|
| > We need more information and research.
|
| You certainly do.
| toomuchtodo wrote:
| You're free to your opinion (legit, no snark intended),
| the market will deliver to the demand. The cost benefit
| ratio is obvious, even accounting for potential side
| effects at scale.
|
| https://www.axios.com/2024/01/18/ozempic-wegovy-weight-
| loss-...
|
| https://www.axios.com/2024/01/19/weight-loss-drugs-
| america-o...
|
| https://recursiveadaptation.com/p/the-growing-scientific-
| cas...
|
| https://www.jpmorgan.com/insights/global-
| research/current-ev...
|
| Edit: I simply do not understand the hostility towards
| this simple intervention, my apologies.
| akira2501 wrote:
| > You're free to your opinion
|
| Oh. Thank you. That's very generous. I assumed we started
| from that position but apparently not.
|
| > the market will deliver to the demand.
|
| Yes, because our healthcare market is perfect, and we
| should acquiesce to it's demands. The same could be said
| of opioid pain killers.
|
| > The cost benefit ratio is obvious
|
| Which entities cost benefit ratio, exactly? The patients?
| Are you _sure_ you have data which allows you to say
| that?
|
| > even accounting for potential side effects at scale.
|
| You're free to your opinion. The market will repeat
| history.
| Teever wrote:
| You seem hostile to this possible solution. Can you
| explain why?
| derektank wrote:
| Obesity rates aren't consistent because access to cheap
| calories is not consistent across the globe. I don't mean to
| be glib, there are certainly other factors, but as a first
| order approximation obesity rates of a region or country are
| going to be proportional to how easy calories are to access,
| followed by how satiating those calories are
| kelseyfrog wrote:
| This is like saying that driving doesn't work because people
| still walk and the real problem is transportation. It simply
| doesn't matter. It's not an argument.
| akira2501 wrote:
| I'm pointing out the problems of considering this a valid
| on term "solution." It's simply not. You need a plan to
| eventually be rid of this compromise.
|
| That GLP-1 has benefits is good. That we could possibly
| rearrange our food system so we don't need it anymore is
| better.
|
| You can acknowledge both without hurting _anyone_. You
| entirely lack an argument.
| pixl97 wrote:
| >That we could possibly rearrange our food system so we
| don't need it anymore is better.
|
| Ya so you want to change a system that involves millions
| of selfish actors and corporations looking to profit and
| that have entrenched themselves, and are protected by
| freedom of association versus a choice between a doctor
| and a patient.
|
| I can tell you which one will be more successful.
| kaibee wrote:
| > It's simply not. You need a plan to eventually be rid
| of this compromise.
|
| because..?
|
| > That we could possibly rearrange our food system so we
| don't need it anymore is better.
|
| Will this be before or after we fix capitalism/finish
| building communism?
| kelseyfrog wrote:
| This is a textbook case of letting better stand in the
| way of good.
|
| I'd love to re-imagine our food of food production and
| consumption, but it sounds like you're arguing that
| because food production and consumption is a better
| solution, we shouldn't be promoting GLP-1 agonists.
|
| Sorry, but one is exists in reality and the other exists
| in our imaginations. When we let our imaginations take
| precedence over reality, we live in a fantasy and the
| consequence is that we get neither. Effectively this
| argues for neither, and that's a bad deal for everyone.
| kbos87 wrote:
| "The [food system] can remain irrational longer than you
| can remain [alive]."
| jmward01 wrote:
| 'problem' is a loaded word. The data is coming in saying that
| this class of drugs provides potentially massive benefits. If
| I get a lot of benefit but didn't fully address the root
| 'problem', I still get a lot of benefit.
| akira2501 wrote:
| As long as the supply chain correctly functions for the
| entire time you plan on being on the drug.
| prepend wrote:
| Yes, obviously. As long as the drug is available and the
| earth exists, etc etc
|
| Therapies are contingent on being available. That's
| uniform. What's unique about glp-1s is that they are very
| effective in weight loss and many other things. As
| compared to alternatives that aren't.
| pixl97 wrote:
| One, going off GLP-1 for all I know doesn't have bad side
| effects, other than going back to your bad diet.
|
| If we are back at the point of supply chain issues that
| interrupt GLP-1 for any significant amount of time you're
| starting to look at issues like we had during covid that
| are going to have all kinds of other effects.
|
| From my understanding getting the pre-compounded
| components isn't that difficult, and that India and China
| are making versions of it now.
| drowsspa wrote:
| Obesity rates consistently increase as people get more access
| to calories.
| smith7018 wrote:
| Yes, but that's an incomplete view on the obesity epidemic
| in the West, imo. It's not just that there's "more access
| to calories," it's that access to healthy foods is getting
| more difficult for a large portion of the population.
| People working multiple jobs don't have time to cook a
| complete, nutritious meal. Also, due to our ever-increasing
| wealth inequality, it's harder for people to afford healthy
| food. A whole chicken, a vegetable, and a starch will
| always cost more than getting something at Wendy's.
| Similarly, a jar of jelly is cheaper and lasts longer than
| a box of strawberries.
| drowsspa wrote:
| I'm Brazilian, but whether you consider Latin America
| western or western-adjacent, here healthy food is
| definitely not cheaper than processed food at all. Yet,
| you can see populations and regions dropping from food
| insecurity directly into obesity as soon as people do
| have access to more food.
|
| The time argument might be relevant, but even then, most
| Brazilians do have cheap and easy access to a very
| healthy lunch in restaurants or to-go meals, purchased or
| prepared, with rice, beans, meat, salad... The breakfast
| is probably bread, but I'd say most people don't eat a
| lot of that in the morning. Getting proper nutrition at
| night will probably be problematic, but it's also a
| smaller window...
|
| But, like I said, processed food is quite expensive here.
| For instance, a 1 kg of chicken breast goes by less than
| a third the price of a McDonald's combo. A pack of
| cookies or snacks will be like double the price of a 1 kg
| of bananas...
| SpicyLemonZest wrote:
| I don't understand your point. Many common medications -
| ibuprofen, albuterol, insulin injections - function entirely
| by hiding symptoms of an underlying problem. If the symptoms
| being hidden are worse than the side effects of the
| medication, what's the concern?
| bigstrat2003 wrote:
| Solving symptoms and not root causes is how you get band-
| aid fixes that wind up being inadequate to the task in the
| end. I would've thought everyone here would be aware of the
| danger of treating symptoms rather than the underlying
| issues, given it's such a common pitfall in the computer
| field.
| moron4hire wrote:
| I think if you reflect on the purpose of a bandaid a
| little bit, you would come to understand why your own
| analogy is bad.
| SpicyLemonZest wrote:
| Again, I genuinely don't understand the point. There's a
| large and well-funded segment of the nutrition industry
| dedicated to solving the root causes - Weight Watchers
| alone has over a billion dollars in annual revenue. We
| just haven't invented a diet-based solution which works
| as well as GLP-1 agonists without requiring you to
| compromise on palatability and feel hungry all day.
|
| It'll be great if we do, although I don't know of any
| promising research avenues and I lean towards the
| hypothesis that the average human metabolism is simply
| tuned to mild obesity under conditions of widespread food
| availability.
| UglyToad wrote:
| The point, which seems to be routinely massively
| downvoted on here, is that both things can be true at
| once:
|
| - these drugs are good and a paradigm shift in the
| treatment of obesity (and have other benefits)
|
| - we must not lose sight of the need to address a
| thoroughly sick food industry that necessitate so many
| people needing to use these. Junk food advertising, lack
| of subsidies for fresh vegetables, HFCS, food deserts,
| etc.
|
| Chile is experimenting with banning junk food ads to
| children and is seeing some early behaviour changes.
|
| The point which people seem to be wilfully missing is
| that we can have both these drugs and advocate for
| cracking down on a food system that deliberately poisons
| everyone in society. Having everyone be on this drug
| because we shrug and say "free market innit" while big
| corps continue to feed us crap is not a solution,
| obviously.
| Sakos wrote:
| "Fixing" the food industry isn't possible for as long as
| they have billions to sink into influencing politics.
| Trying to find a market or political solution has failed.
| Full stop. The fact that you're still trying to find some
| way to make it work is embarrassing and depressing. It's
| time to attack the problem from another direction, one
| that will also ensure these companies either go bankrupt,
| lose relevance and power and/or evolve into a form that's
| less parasitic and more beneficial to us as a species.
| GLP-1 can be one tool to help us do that.
| Attummm wrote:
| That is because the advice around eating less is focused on old
| paradigms that have clearly failed.
|
| Those drugs let people experience intermittent fasting and
| fasting by reducing hunger and snacking.
|
| The danger of suppressing hunger signals is that hunger
| could've been a important que for nutritional needs.
|
| Muscle loss is severe danger of gpl-1, And muscle size is tied
| to longevity.
|
| So although promising it's not without danger. And there are
| other paradigms but those are not yet explored yet the
| underlying mechanisms work the same.
|
| Edit: Let's keep HN a place where discussion can be held
| without just kneejerk down voting.
|
| Edit2: great discussion thanks all.
| stavros wrote:
| > Those drugs let people experience intermittent fasting and
| fasting by reducing hunger and snacking.
|
| This shows you haven't tried GLP-1s. I've been doing IF for
| ten years, doesn't stop me from being overweight. GLP-1s do.
| Attummm wrote:
| First of all congratulations with your succes, and not take
| away from that. But IF nor fasting is a silver bullet.
|
| Reducing food intake, and insuline while keeping hunger
| down is.
|
| Important aspect is keeping hunger down. And if your
| fasting/excersicsing you can experience the same.
|
| The discussion on weight unfortunately almost always
| focused on total weight.
|
| But we would like to retain our muscles, and reduce adipose
| tissue(fat).
|
| With gpl1 people are able to fast, stop snacking and reduce
| food intake because hunger signals are blocked.
|
| But a fasting lifestyle, which goes further then just IF.
| And a focus on nutrition(vitamins, minerals, quality
| sources) could the same.
|
| Furthermore the effects of lowering inflammation of gpl1 is
| only logical reduction in food intake/fasting will lead to
| autophagy.
|
| IF/Fasting and other new nutritional paradigms are still
| new and uncharted. It's not clear yet what the full effects
| are, and how to implement them correctly.
| stavros wrote:
| Yeah, but at the end of the day, it either works, or it
| doesn't. You can say "you're holding it wrong" all you
| want, but if it's easy to hold the thing wrong, it's the
| thing's fault.
|
| GLP-1s work for many more people than any other diet
| advice we've ever had.
| Attummm wrote:
| IF is not well understood, nor explained.
|
| So in that aspect we agree completely. A few years ago
| people would call you mad for fasting, and now we have
| drug that allows people to life the fasting lifestyle.
|
| And if there is a medical reason I'm not making the
| argument against. I'm making the argument that it's a
| intervention and that healyhy nutrition, healthy
| relationship with food will is the long-term solution.
|
| And order todo that we would need to explore other
| nutritional paradigms than the current one.
|
| Edit: - Fasting lifestyle, like omad(eat once a day)
| removes the feeling of hunger and thoughts about food,
| until it's the moment to eat.
| stavros wrote:
| > So in that aspect we agree completely. A few years ago
| people would call you mad for fasting, and now we have
| drug that allows people to life the fasting lifestyle.
|
| It's nothing like the fasting lifestyle, it just quiets
| the food noise.
|
| > I'm making the argument that it's a intervention and
| that healyhy nutrition, healthy relationship with food
| will is the long-term solution.
|
| That's like saying "I'm making the argument that diabetes
| medication is an intervention, and that producing healthy
| amounts of insulin is the long-term solution". Yeah, it's
| all well and good, _except it doesn 't work_.
|
| You can yell at people for not <insert favorite reason
| here>, but, at the end of the day, people have tried
| diet, they've struggled with it, and it's failed. No
| matter how much yelling you do, they won't stop. It's
| like trying to talk a meth addict out of their addiction.
| bb88 wrote:
| Doctors have long said, "Diet and Exercise", but they
| couldn't really address the pain aspect of hunger until
| the last few years.
|
| And hunger is painful.
|
| Hunger is something that is left to the patient to cope
| with -- usually badly. Sure there could be support groups
| and exercise groups, but nobody is going to be there in
| your bed when you're trying to fall asleep with hunger
| pains.
| stavros wrote:
| This thread is kind of painful because it's full of
| people who have no problem with their weight telling
| others to "just don't have a problem too!".
|
| I don't eat because I'm hungry. I eat because food is
| there, or because I remembered that food exists, or
| because I have nothing better to do, or because stuff
| tastes good. I can't remember the last time I was hungry.
|
| The weird thing is I can go a _really_ long time without
| food. I can go 36 hours easily without eating something,
| hunger doesn 't bother me at all. After 36 hours, I think
| "huh, I should probably eat something".
|
| Such situations where I forget to eat are really, really,
| really rare. I have to basically be on my own and working
| on something fun, because that's when I both don't have
| food in the house and don't want to spend the two minutes
| it takes to order something.
| bb88 wrote:
| Exactly.
|
| Kids who went hungry at school had behavioral problems,
| and couldn't focus on schoolwork. The solution was to
| give the kids breakfast, not to tell them to cope with
| hunger until they got home.
| sangnoir wrote:
| Depending on ones metabolism, IF with no caloric deficit
| doesn't guarantee weight loss.
| bb88 wrote:
| Right and caloric deficit is just diet.
| schnebbau wrote:
| You don't lose weight when IF if you eat your maintenance
| calories during the period you're not fasting.
| RachelF wrote:
| A GLP-1 drug trial 12 years ago by a major pharma company was
| stopped because of increased suicide risk (2 in 10,000) among
| the cohort.
|
| We will see what happens long term the second time around.
| chpatrick wrote:
| It's not even the second time around now, liraglutide was
| approved a decade ago.
| vineyardmike wrote:
| If people are obese, they're not getting the right hunger
| signals anyways. Obesity is _heavily_ tied to longevity.
| GLP1s cause muscle loss because when you lose weight, some of
| your caloric deficit will be supplemented by your muscles.
|
| The article suggests that non-weight loss side effects of
| GLP1s are also worth considering taking the medication for.
| If you're maintaining a healthy weight, while taking the
| drug, you shouldn't experience the muscle atrophy.
|
| Also, _muscle size_ isn't tied to longevity, usable muscle
| and a certain strength and physical ability is tied to
| longevity. Muscle size is a convenient proxy. Also
| cardiovascular ability in a related way. You basically just
| need to be able to move and carry things and act in your
| environment in a responsible way at an old age so you don't
| fall or hurt yourself.
| ryanobjc wrote:
| I came here to basically say this.
|
| People who tout the dangers of glp1 - and there ARE risks!
| - are also ignoring the "what did you do instead of a glp1"
| and the answer is.... remain overweight, which has many
| risks!
|
| Yes glp1 might increase the risk of a certain kind of
| cancer. But guess what, it also reduces the risks of many
| other cancers tied to obesity!
|
| It's hard for me to take hand-wringing over glp1s
| seriously. Appeals to "JUST do x" are lost in the "just" -
| hello if people could just do intermittent fasting, or eat
| less calories, well then there would be less obesity. The
| obesity epidemic is literally a rebuttal to any of these
| arguments.
| Attummm wrote:
| Your points are just reforcing my initial point. Old
| paradigms of nutrition have clearly failed. If we could
| acknowledge that we could move forward and be open to very
| promosing alternative paradigms.
|
| Which currently are not studied enough, to create clear
| nutritional guidelines for the public.
|
| Gpl1 and those paradigms work through the same mechanisms
| action (autophagy, ketones, reducing food intake).
|
| If there is acute problem with health such as
| (morbidly)obesity then gpl-1 could be a great intervention.
|
| But its not long term solution, nutrition and a healthy
| relationship with food and lifestyle is.
|
| Muscles are very important for health, but let's not go
| into that. For muscle size I linked to meta study about
| muscle size and all cause mortality (longevity)
|
| > Conclusions: Low SMI(skeletal muscle mass Index) was
| significantly associated with the increased risk of all-
| cause mortality.
|
| https://pubmed.ncbi.nlm.nih.gov/37285331/
| vineyardmike wrote:
| > Old paradigms of nutrition have clearly failed. If we
| could acknowledge that we could move forward and be open
| to very promosing alternative paradigms.
|
| > Which currently are not studied enough, to create clear
| nutritional guidelines for the public.
|
| We have very clear, very obvious nutritional guidelines
| for the public, and we have lots of research on the
| healthy food to eat. The TLDR guidelines that would have
| a positive impact on most people is "eat less". Doesn't
| seem to work, and it's not an informational problem.
|
| (1) its not long term solution, nutrition and a healthy
| relationship with food and lifestyle is.
|
| The reality is that plenty of people will just _never_
| have this. Some people are "weak" or "genetically
| predisposed" or "addicted" or "impoverished" or any other
| number of things that people use to explain poor diet. No
| amount of nutritional guidelines will fix this. That's
| just the (unfortunate) reality. Now what do we do?
|
| (2) GLP-1 medication (according to the article) have
| other benefits beyond nutrition, eg addiction,
| Alzheimer's, kidney health, etc. These benefits could be
| very real (some are still being studied). If they turn
| out real, how does our relationship with the drug change,
| how that its not just a replacement for a "healthy
| relationship with food and lifestyle"?
|
| You've mentioned muscle being a proxy for health. Do you
| consider going to the gym and working out to be a "long
| term solution"? Why is spending an hour a day performing
| an artificial activity (lifting weights) generally
| considered a healthy lifestyle, but taking safe
| preventative medication not considered part of a healthy
| lifestyle?
|
| (Generally) society considers vaccines to be safe and
| healthy, and we recommend them for everyone from a young
| age. They're obviously quite artificial, and they trick
| our body by stimulating certain biological pathways
| artificially.
|
| What is different about certain medication like GLP1 meds
| that keep us from considering it part of a safe, healthy
| lifestyle?
| Attummm wrote:
| The health benefits of eating less and fasting such as
| autophagy, ketones occurs with or without gpl1. That is
| how gpl1 is healthy, because eating less and fasting is
| healthy.
|
| You don't have to go to the gym to activate and stimulate
| muscles. But our bodies are made for daily usage of
| muscles.
|
| We always had downtrodden, poor, weak people, in any
| society. But in the 1970's they were not obese.
|
| We dont take daily vaccins they are a intervention. Gpl1
| could be intervention for obesity patients.
|
| The danger of long term usage of gpl1 is that our bodies
| emerged ecosystems that we don't understand yet. By
| reducing hunger signals that their motivate a person to
| get nutrition such as protein, vitamins and minerals, etc
| Leads to malnutrition, muscle loss and other diseases.
|
| Your point is that there is no problem with current
| paradigm of nutrition while at the same time promoting a
| agent that stops the addictive nature of our current
| nutritional paradigm.
|
| If you use gpl-1, And it works for you that is great and
| we should be grateful that gpl-1 is available. My only
| advice would be, to lift weights or callisthenics to keep
| your muscle size and strength. And to explore other
| nutritional paradigms that can help you maintain the
| weight loss without gpl-1.
| illiac786 wrote:
| On one side, sure GPL-1 may have side effects, maybe bad
| ones. On the other hand, overweight in the sense of excessive
| adipose tissue, correlates with a huge number of very bad
| health problems (both mental and physiological), with an
| abundance of proof around causality for many of these.
|
| I'm thinking, whatever negative side effects we find for
| GPL-1 in the future, they will have to be pretty massive to
| offset all these benefits.
| thefz wrote:
| Eating less works, if taking a drug that makes you eat less,
| well, works.
| maxerickson wrote:
| That's a bad read of what they said. They didn't that eating
| less doesn't work, they said that telling people to eat less
| doesn't work.
|
| I am tempted to make a snide remark, but I suppose that won't
| do any good.
| derbOac wrote:
| I'm fine with GPL-1 agonists, they seem great, not trying to
| argue against them.
|
| This is an age old problem in the obesity treatment and
| research community. It never seems to go away. It's come up
| with bariatric surgery, with other methods, and now GPL1-
| agonists.
|
| The issue for me is that "telling people to eat less" is sort
| of a strawman in some ways. It _doesn 't_ work.
|
| What _does_ work, however, at least according to evidence I 've
| seen, is giving people strategies for losing weight, therapy,
| support, and so forth. It doesn't work for everyone but it does
| for some.
|
| I would rather people try that first as it can be self-
| sustaining and doesn't require medication.
|
| I'm not opposed to the medication or people using it, in fact I
| think it's a good thing, but it seems a little dangerous to me
| to create a culture where people are just told "take this pill,
| pay lots of money for it, because nothing else will work" which
| is not actually true. I don't think we're at that point but
| it's easy for me to imagine.
| ZYbCRq22HbJ2y7 wrote:
| Except adherence to taking GLP-1 agonists isn't a given,
| especially with dosing regimens that are shorter than a week.
| devit wrote:
| What about people who, with their current habits, are on the
| bottom range of what is considered "normal" weight (in the BMI
| sense) or already underweight?
|
| Wouldn't taking GLP-1 agonists (for potential non-weight-loss
| benefits) be potentially harmful as it may reduce eating even
| further and lead to being significantly underweight?
| riwsky wrote:
| They just need to take GLP+1, instead.
| throwup238 wrote:
| It's the number one recommended supplement by the American
| Society for Cannibals. The flavor is in the fat!
| kubectl_h wrote:
| > Wouldn't taking GLP-1 (for potential non-weight-loss
| benefits) be potentially harmful as it may reduce eating even
| further and lead to being significantly underweight?
|
| Almost certainly at the weight loss dosages people are taking
| now, but semaglutide (at least) can be tuned up and down for
| effect. Time will tell what kind of dosage is required for
| these non-weight-loss benefits.
|
| That said, I think it's more important to focus on how this
| drug works -- it works in the brain and in specific areas of
| the brain that we now know are important for weight
| loss/addiction/inflammation(?) (because of these emergent
| miracle drug effect). It doesn't seem outside the realm of
| possibility that drug companies will be able to target these
| systems with more finesse in the future as opposed to
| superdosing engineered stable GLP-1 molecules that flood the
| system.
|
| It is the future understanding of what this drug does that is
| the real promise for all people -- we are just in the early
| stages of understanding what we've found.
| loeg wrote:
| Sure, it would probably not be helpful to give these people
| medical anorexia unless there was some huge, huge, more-than-
| offsetting other benefit. (Less than 2% of the US population is
| considered underweight by BMI: https://www.kff.org/other/state-
| indicator/distribution-of-bo... . )
| nonameiguess wrote:
| If it really is inflammation, exercise targets that just as
| well, and also acts as a miracle drug that seems to reduce the
| risk of just about everything, somewhat paradoxically even
| orthopedic injuries over a long enough timescale (because you
| stave off age-related muscle and bone mineral loss).
|
| But that puts us back in the "telling people to exercise
| doesn't cause them to actually do it" at the public health
| level. For you yourself, you can simply live a less risky,
| healthier life. For all yous, probably we need something like a
| once-weekly pill or injection that doesn't require drastic
| habit changes. For all of society on a forever timescale, of
| course, we can ignore the fact that adults won't change their
| ways and focus on instilling lifelong athlete habits in kids.
| Doesn't seem to be the direction we're going in, though.
| pixl97 wrote:
| Things like GLP-1 can give a near immediate bodily response
| that can lead to people starting to work out. When you have
| inflammation issues I can promise the last thing you want to
| do is put stress on your body from working out. Especially
| when most people don't know how to do it properly.
| leetnewb wrote:
| Obviously subject to conversation with their doctor, but my
| endocrinologist suggested against this class of drugs for blood
| sugar control.
| riwsky wrote:
| I used GLP-1 to prepare my taxes last week, it was such a stress-
| free experience.
|
| Then as I was coding I kept hitting context window limitations
| with o1-preview. so on a lark I just fired up my local Ozempic
| and submitted the same prompts and bam: spit out a whole working
| iOS app first try.
|
| I heard that before they nerfed it with RLHF, Mounjaro not only
| treated diabetes but also made you charming in conversation and
| sublimely compassionate towards all beings.
|
| The future is now
| haccount wrote:
| Guys hear me out. The next VC funded killer idea:
|
| ChatGLP!
| milliams wrote:
| What's GLP-1?
| philipkglass wrote:
| In this context it's shorthand for "GLP-1 receptor agonist."
|
| https://en.wikipedia.org/wiki/GLP-1_receptor_agonist
|
| _Glucagon-like peptide-1 (GLP-1) receptor agonists, also known
| as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of
| anorectic drugs that reduce blood sugar and energy intake by
| activating the GLP-1 receptor. They mimic the actions of the
| endogenous incretin hormone GLP-1 that is released by the gut
| after eating._
| kbos87 wrote:
| The best way that I can describe what Semaglutide has done for me
| is that I feel like almost nothing in my life has changed (other
| than being down 45lbs, suddenly having normalized liver enzyme
| levels and blood pressure.) Before starting it, I generally ate
| until I was satiated, almost never over full. From time to time
| I'd maintain a caloric deficit, but it meant a large part of my
| attention was consumed, day and night, by a nagging distraction
| of food.
|
| Today, I still just eat a normal diet until I'm satiated - but
| 1/3 of the food is left on the plate. I have a little less of an
| interest in alcohol and coffee, but other than that it's like
| nothing has changed.
|
| My point is that there's still a common sentiment that these
| drugs are some sort of a shortcut for people who want the ability
| to over-indulge, when in reality that couldn't be further from
| the truth.
|
| I think what I feel like on a GLP-1 is what most people feel like
| without one. If you want to know what I feel like without a
| GLP-1, try not eating until your mind is constantly nagging you
| to do so - then try staying like that forever. That's what a lot
| of people propose to anyone who has a problem with their weight.
| 404mm wrote:
| I assume you are also on weekly doses. How does it work for
| you?
|
| I feel like I go through cycles of:
|
| Day 1: no change
|
| Day 2: can go whole day without eating, a bit nauseous
|
| Day 3-5: feeling bloated, food doesn't digest fast, not eating
| much, biggest weight loss
|
| Day 6-7: Slowly getting back to eating reasonable portions
| bb88 wrote:
| That's usually how it works for me too. I find that days 2-5
| I start feeling not very good. I wouldn't say bloated, but
| almost weird blood sugar levels.
|
| Usually about 6pm in the evening is when I start feeling
| terrible. Kinda makes me want to eat less.
| hbosch wrote:
| It works much better, in my experience, to cut the dose in
| half and take it twice a week. I do Sunday and Thursday,
| 2.5mg of tirzepatide per injection.
| Salgat wrote:
| This is my issue. I have lost 40-60lb many times in the past 15
| years, but I always gain it back because the root cause is not
| fixable. I always have a lingering hunger, and I don't want to
| spend my entire life hungry.
| andrewmcwatters wrote:
| It feels more likely to me that there's some sort of condition we
| don't have a widely known name for that is caused long-term by a
| combination of predisposition in genetics and something in
| western diets that is, I'm not sure, forcing us to overproduce
| ghrelin (possible links to puberty occurring earlier in both
| young boys and girls?), or underproduce certain classes of
| incretins (possible links to excessive blood sugar levels in
| larger percentages of the population historically over time?).
|
| It would be boring to learn that it's just caused by excessive
| exposure to fructose.
|
| But what do I know, I'm just a dumb HN reader.
|
| Seems neat that there's ongoing work in this area and it'll be
| cool to read about new knowledge in that space when something is
| discovered.
| avelis wrote:
| > FTA: So we're not only going to be treating (or outright
| preventing) a number of diseases, we're going to be learning more
| about the cause of these diseases than we ever did before.
|
| Ultra processed foods (UPF) needs a hard look IMO. It's the
| leading cause of many diseases stated in the article and several
| others including cancer and dementia.
| dyauspitr wrote:
| This is probably what's going to get us over the 80 years life
| estimate plateau. The main killers now are overwhelmingly
| cardiovascular diseases and cancers.
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