11 ms·

GLP-1 for Everything

• mentos 2y ago
  Isn’t this just eating less food is good for everything?
  • api 2y ago
    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 2y ago
    Yes. Turns out everyone should have just been eating fats all along.
    • fredgrott 2y ago
      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 2y ago
        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 2y ago
        > 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 2y ago
    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 2y ago
      There have previously been associations between caloric intake and Alzheimer Disease or Cognitive Aging, for example: https://jamanetwork.com/journals/jamaneurology/fullarticle/782575 https://jamanetwork.com/journals/jamaneurology/fullarticle/7... https://www.pnas.org/doi/10.1073/pnas.0808587106 https://www.pnas.org/doi/10.1073/pnas.0808587106
      • Etheryte 2y ago
        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 ϵ4 allele. > The hazard ratios of [Alzheimer Disease] for the highest quartiles of calorie and fat intake compared with the lowest quartiles in individuals without the apolipoprotein E ϵ4 allele were close to 1 and were not statistically significant. For the general population, there was no correlation. Identifying specific genetic outliers where there may be a connection is still useful, but far from a general result.
    • arijo 2y ago
      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/ 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 2y ago
        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.
  • slaymaker1907 2y ago
    Depends on who you are and if you have an eating disorder.
  • didgeoridoo 2y ago
    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 2y ago
      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 https://en.wikipedia.org/wiki/Illusion_of_control
      • didgeoridoo 2y ago
        You’re going to have to be more specific, because I am sure you are not arguing against the concept of medicine.
        • breck 2y ago
          [flagged]
          • malfist 2y ago
            Try telling a type 1 diabetic patient to eat like it's the 1800s
            • 2y ago
  • david-gpu 2y ago
    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 2y ago
      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 2y ago
        Add me to that sample set, I drink far, far less with it
      • akira2501 2y ago
        > 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 2y ago
          > 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.
  • loeg 2y ago
    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.
  • ZYbCRq22HbJ2y7 2y ago
    No, there are a number of effects of GLP-1 RAs that are not directly related to their initial research and development associated with insulin response, beta cells, etc or recent research associated with appetite suppression. For instance, there is growing research and speculation around dopamine systems in humans. It might be awhile before the research propagates to the realm of popular science. IMO, it kind of represents how incredibly blind we are to supposedly safe compounds, and how arrogant others are for calling for less regulation. When attention is high, suddenly so much more is revealed.
• erulabs 2y ago
  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.
  • deleted 2y ago
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  • modeless 2y ago
    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?
    • deleted 2y ago
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  • andrewmcwatters 2y ago
    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 2y ago
  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 2y ago
    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 2y ago
    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 2y ago
    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.
• levocardia 2y ago
  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 2y ago
    > 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 2y ago
      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 2y ago
• Traubenfuchs 2y ago
  [flagged]
  • eli_gottlieb 2y ago
    No. Some of the positive effects of GLP-1s are seen before the actual weight-loss occurs.
    • Traubenfuchs 2y ago
      A healthy diet and lifestyle lead to increased GLP-1 levels. Were there actually any studies on their effect on healthy and fit people? Loss of muscle mass is already recognized: https://pubmed.ncbi.nlm.nih.gov/38937282/ https://pubmed.ncbi.nlm.nih.gov/38937282/ And probably especially bad in people without fat reserves.
• cschmidt 2y ago
  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-ozempic-are-among-the-most-important-drug-breakthroughs-ever 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-obesity-drugs-like-ozempic-will-change-the-world https://www.economist.com/leaders/2024/10/24/its-not-just-ob... (sorry, paywalled)
  • toomuchtodo 2y ago
    https://archive.today/D06ZN https://archive.today/D06ZN https://archive.today/YgiWx https://archive.today/YgiWx
  • RachelF 2y ago
    This can also be viewed as advertising - there are board members in common between The Economist's holding company and Novo N.
• jpadkins 2y ago
  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 https://en.wikipedia.org/wiki/Systemic_inflammation
• kelseyfrog 2y ago
  The main difference between GLP-1 agonists and telling people to eat less/better is that one works and one doesn't.
  • akira2501 2y ago
    Obesity rates are not consistent across the world or time. Neither work. They just hide symptoms of the larger problem.
    • toomuchtodo 2y ago
      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 https://news.ycombinator.com/item?id=41989101
      • akira2501 2y ago
        > 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 2y ago
• devit 2y ago
  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 2y ago
    They just need to take GLP+1, instead.
    • throwup238 2y ago
      It's the number one recommended supplement by the American Society for Cannibals. The flavor is in the fat!
  • kubectl_h 2y ago
    > 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 2y ago
    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-body-mass-index-among-adults/ https://www.kff.org/other/state-indicator/distribution-of-bo... . )
• riwsky 2y ago
  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 2y ago
  Guys hear me out. The next VC funded killer idea: ChatGLP!
• deleted 2y ago
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• milliams 2y ago
  What's GLP-1?
  • philipkglass 2y ago
    In this context it's shorthand for "GLP-1 receptor agonist." https://en.wikipedia.org/wiki/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 2y ago
  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 2y ago
    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
    • deleted 2y ago
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    • bb88 2y ago
      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 2y ago
      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.
• deleted 2y ago
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• andrewmcwatters 2y ago
  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 2y ago
  > 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 2y ago
  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.
• explodingman 2y ago
  Love that word "pleiotropic", nice vocab builder. So it looks like GLP-1 may have positive side-effects beyond what can be explained as consequences of weight loss. Surprising linkages between biochemistry/hormones and temperament. I am slowly (1 kilogram per month) losing weight by eating nothing but meat 2-3 days per week. My understanding is that the extra GLP-1 secreted by the gut when digesting lots of protein leads to appetite suppression. It works, and is surprisingly easy to do (no feelings of hunger). So will I also be getting the beneficial side effects of GLP-1? If so, high-protein dieting becomes the smart way to lose weight.
• brvRXZ 2y ago
  GLP-1 seems to inhibit the production of glucagon, which should directly reduce the amount of glucose in blood, which is a desired effect for treating obesity. On the other hand, it seems to stimulate insulin production, which also reduces glucose, but extra insulin may cause insulin resistance, which can contribute to type II diabetes. Insulin resistance can take years to develop, so maybe you should test for that if you use GLP-1 long term.