[HN Gopher] GLP-1 drugs linked to lower death rates in colon can...
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       GLP-1 drugs linked to lower death rates in colon cancer patients
        
       Author : gmays
       Score  : 212 points
       Date   : 2025-11-12 19:50 UTC (1 days ago)
        
 (HTM) web link (today.ucsd.edu)
 (TXT) w3m dump (today.ucsd.edu)
        
       | bicx wrote:
       | Maybe I'm just an aging cynic, but I'm waiting for the other shoe
       | to drop when it comes to GLP-1s. There have been so many claims
       | of positive benefits that it almost seems too good to be true.
       | With them being so expensive, the producers have every incentive
       | to upsell using any study they can get their hands or money on.
       | 
       | If it's all upside, then I'm happy to be wrong.
        
         | bitwize wrote:
         | Haven't you been reading Hackernews for the past 10 years?
         | Sugar has been implicated in pretty much every major late-life
         | disease, and the closest thing to a cure before GLP-1 agonists
         | was fasting.
        
           | phantasmish wrote:
           | ... and the mechanism by which GLP-1s cause weight loss is,
           | more or less, by making fasting really easy.
        
           | lm28469 wrote:
           | That's such a lazy and unimaginative take that basically
           | skips 99.999% of human history during which sugar wasn't a
           | problem at all.
        
             | tengbretson wrote:
             | The baseline lifestyle of 99.999% of human history would,
             | by modern classifications, be considered intermittent
             | fasting.
        
             | jimbokun wrote:
             | That was the part of history when humans didn't have much
             | access to cheap sugar.
        
             | Der_Einzige wrote:
             | You're the lazy one.
        
           | pessimizer wrote:
           | Hacker News has extreme orthorexia and endorses all sorts of
           | quackery.
        
         | robbomacrae wrote:
         | There have been some. I've heard about eyesight related issues.
         | A quick google found this article [0] where results showed that
         | people using GLP-1 drugs were 68.6 times more likely to develop
         | certain types of vision problems.
         | 
         | [0]: https://www.aao.org/newsroom/news-releases/detail/do-
         | glp-1-d...
        
           | phantasmish wrote:
           | A lot of the issues are hydration-related, and I wouldn't be
           | surprised if the eye ones are, too. Some water intake is from
           | food, so if you eat less, you need to drink more. If you also
           | tend to drink with food, and you're eating less, you may
           | drink less instead of the _more_ that you need to be. Add in
           | a generally dulled "I crave something" sense and you've got a
           | recipe for not just going all day without eating, but also
           | without _drinking_.
        
             | mock-possum wrote:
             | I'm not a doctor but iirc water consumed along with a meal
             | is absorbed slower and therefore results in longer-lasting
             | hydration - than just a bare glass of water on an empty
             | stomach. Of course, eating might add more material that
             | encourages dehydrating, so I don't know if you'd get a net
             | benefit from a bag of teriyaki beef jerky say.
        
           | azinman2 wrote:
           | This is also an extremely rare vision problem. So absolute
           | numbers are very tiny. The absolute numbers for diabetes,
           | weight related problems, etc far dwarf this.
        
             | robbomacrae wrote:
             | Right. On the whole I think these things are incredible..
             | looking to try myself after reading here in HN the other
             | day about it working for all sorts of distractions. Just
             | wanted to point out it's not all sunshine and rainbows
             | which would certainly be suspicious.
        
               | azinman2 wrote:
               | Literally too much water or aspirin can kill you. Some
               | people are allergic to avocados. Driving kills huge
               | numbers of people daily. Everything is about risk/reward,
               | and looking at the macro picture. And right now the
               | comorbidities for obesity are terrible in huge absolute
               | numbers... something that GLP-1's can take down in
               | significant magnitude. Unless we learn that the majority
               | of users end up with something worse than obesity,
               | they're a huge win for public health.
        
           | asmor wrote:
           | A large drop in HbA1c does cause early worsening of diabetic
           | retinopathy. Regardless of how it's achieved. So expect some
           | noise in generalized data.
           | 
           | Personally, I went from mild background retinopathy to PDR
           | and getting laser treatment in about 3 months. My
           | ophthalmologist (who has an academic background) didn't
           | really know if this diagnosis had the same "quality" of
           | someone who "naturally" progresses to PDR, but some studies
           | say it's transient.
        
           | projektfu wrote:
           | It's a little suspicious... 68x risk with semaglutide, no
           | significant risk with tirzepatide. Case-control studies that
           | merely search these databases are only really useful for
           | hypothesis generation.
        
         | bpodgursky wrote:
         | GLP-1s are just showing what people always knew to be true but
         | was not clinically actionable -- most of our health problems
         | come from eating too much and being fat.
         | 
         | Well, now it's actionable. No magic, just adherence.
        
           | degamad wrote:
           | We don't quite have the data to say "most" yet, but it's
           | certainly looking like "many" is justifiable.
        
         | infecto wrote:
         | I don't know. Having listened to a number of interviews with
         | some of the founders in this area of drug research I came away
         | with a much higher respect and significantly less cynicism
         | toward big pharmaceutical. Novo Nordisk is run by a nonprofit
         | even.
        
         | gwbas1c wrote:
         | Some people stop using it due to personality changes.
        
           | matthewdgreen wrote:
           | Say more?
        
           | ilikecakeandpie wrote:
           | Yeah I stopped because I didn't like the way it made me feel.
           | I needed it because my blood sugar was way too high and it
           | helped me drop close to 60 pounds in 6-8 months, but I did
           | not like how it made me feel and I lost more muscle than I
           | was happy with.
           | 
           | I've gained about 15-20 pounds back, but I'm now much
           | healthier overall.
           | 
           | I like how my brain works and I didn't like something
           | affecting or changing that because I couldn't put the fork
           | down. Easy decision for me
        
             | AndrewDucker wrote:
             | I'd be interested to know how it changed you.
        
             | CoastalCoder wrote:
             | Is it possible that some of that personality change was
             | because you were running a calorie deficit?
             | 
             | I'm not dismissing your overall point. I minimize my use of
             | Adderall for that very reason.
        
         | helicalmix wrote:
         | I think it's totally fair to be skeptical, but it's also not
         | rare to have interventions that are astoundingly effective.
         | 
         | Antibiotics and vaccines may not be completely free lunches,
         | but they're very good at what they do.
        
         | piker wrote:
         | The fact is though that but-for taking the drugs a lot of the
         | folks that take these things would be long dead before, say,
         | the GLP-1 induced cancer kicked in.
        
         | ecshafer wrote:
         | GLP-1s have been peescribed for like 20 years, but have been
         | limited more to diabetics and extreme cases. So there is pretty
         | good data. Not to say there isnt going to be side effects in
         | some population sample, but we need to compare that with
         | obesity and diabetes (which is a very bad disease).
        
           | Cthulhu_ wrote:
           | But also do long-term studies; one thing I gathered
           | (anecdotal through the internet so take it with a grain of
           | salt) is that people revert to their old habits when they
           | stop taking it. Not always, of course, and I think using it
           | should always be done with guidance of a dietician etc to
           | make lifestyle adjustments if needs be, but it did imply that
           | long term usage is a factor that needs to be considered.
        
           | hollerith wrote:
           | SSRIs have been prescribed for 37 years, and society is just
           | starting to understand that under current prescribing
           | protocols, they do more harm than good.
           | 
           | Also, isn't the dose used to treat obesity 3 times higher
           | than the dose used over those 20 years to treat diabetes?
        
         | OptionOfT wrote:
         | Even with an increased risk of mortality, at least right now I
         | can live. The voice in my head that is constantly telling me
         | I'm hungry is quiet.
         | 
         | Without it I'd die sooner anyway.
        
           | stavros wrote:
           | It's not even "I'm hungry", it's just "must have more food".
           | What a nuisance.
        
             | rootusrootus wrote:
             | Exactly. Food noise is a terrible nuisance. "Go eat." "Umm,
             | I don't feel hungry." "Doesn't matter, eat anyway."
             | 
             | Having that on a repeat loop is no fun. Getting rid of it
             | is worth all of the mild side effects and cost.
        
               | stavros wrote:
               | 100% agreed. It would be nice if I lost some weight, but
               | just not having the food noise is worth it.
        
         | radial_symmetry wrote:
         | Most medications have negative side effects because otherwise
         | our bodies would already have whatever changes they make
         | through evolution. My personal theory (based on nothing but my
         | own intuition) is that GLP-1s are an adaptation to the modern
         | world that evolution hasn't caught up with yet.
        
           | ammon wrote:
           | And we know what the adaptation is: calorie constraint. We
           | evolved in a calorie constrained environment. We don't live
           | in one now. Our set point for desire to eat is clearly too
           | high. None of this means that glp-1 inhibitors don't have
           | other side effects, of course.
        
           | lm28469 wrote:
           | > Most medications have negative side effects because
           | otherwise our bodies would already have whatever changes they
           | make through evolution.
           | 
           | That's not what evolution is, at all
        
             | dillydogg wrote:
             | This sounds like the argument during the pandemic, "If
             | masks work, then why didn't we evolve permanent masks?
             | Checkmate atheists." Though I do understand the impulse
             | that evolution is working towards some unknowable
             | perfection because of how I was taught evolution during
             | high school, that is, of course, not how it works.
        
           | viking123 wrote:
           | lol
        
         | gedy wrote:
         | At this point I view the risks/downsides as akin to vaccines.
         | Sure things happen, the overwhelming positives greatly outweigh
         | this.
        
         | unsupp0rted wrote:
         | Not everything has another shoe to drop.
         | 
         | Getting people to eat more broccoli is almost entirely upside.
         | Sure a handful of people will be allergic or whatever, but on a
         | population level some interventions are just one positive after
         | another, and there's no reason it has to be a deal made with
         | the devil.
        
           | cerved wrote:
           | Well glp1 doesn't make you want to eat broccoli. Just less in
           | general
        
             | daedrdev wrote:
             | sure but it definitely makes carbs specifically disgusting
             | in my case
        
               | stavros wrote:
               | I can confirm that. On GLP-1s (when they worked for me,
               | anyway), I'd routinely think "pizza? Bleh, so fatty, I'd
               | really like some chicken breast with roast potatoes
               | instead right now".
        
               | dfc wrote:
               | You can confirm that GLP1s make "carbs specifically
               | disgusting" and an example of this reaction is that you
               | would have a desire to eat potatoes?
        
               | stavros wrote:
               | Oh no, you have torn through the flaws in my argument
               | like bullets through paper, however will I live this
               | down? Unless I clearly meant "it makes previously-
               | desirable food undesirable", anyway.
        
               | dfc wrote:
               | I was not trying to tear your argument down. The comment
               | you replied to was about carbs being specifically
               | disgusting and in my head potatoes are the runner up to
               | bread for classic examples of carbs. I was simply asking
               | about what seemed like a contradiction. I have been
               | looking into GLP1s and have not seen/heard people mention
               | that GLP1 make carbs gross.
        
               | stavros wrote:
               | I think it varies per person. For me, it didn't
               | specifically make carbs gross, but it did make unhealthy
               | food less palatable. I think that's what the GP was
               | talking about as well, they were just a bit more
               | specific.
               | 
               | It really depends on the person, though. They worked for
               | me for a while and don't work now, but I'm a small
               | minority, from what I've heard from people. When they
               | worked, they were great.
        
             | rootusrootus wrote:
             | Actually there is a very real effect on which foods you
             | find appealing and which ones are kind of gross. It's a
             | thing the food companies have been studying, and their own
             | studies show that people on GLP1s tend to skip the junk
             | food aisle and head towards the produce section instead.
        
               | 01100011 wrote:
               | Oddly enough semaglutide is making me crave sugar more.
               | It might be the frequent sensation of having low blood
               | sugar. Idk.
               | 
               | It does make me choose more dense meals though since I
               | know I can't eat that much due to delayed gastric
               | emptying. But I have to budget some room for prunes to
               | counteract the constipation. It definitely makes you
               | think about what you eat.
        
               | skissane wrote:
               | Tirzepatide somehow gave me a craving for apples. I used
               | to occasionally eat them, now I eat them every day.
        
           | CalRobert wrote:
           | I do get a bit gassy if I binge on broccoli...
        
         | jesse_dot_id wrote:
         | Same. I think that pharmaceutical industry is lot more bleak
         | now than it was when Fen-Phen became popular. GLP-1 usage is
         | largely off-label as far as I know, but I wouldn't trust them
         | even if it wasn't. There is a mountain of precedent for these
         | companies to choose profit over health, and for our
         | government(s) to aid them in covering up evidence of negative
         | effects on the latter for the sake of the former.
        
           | topato wrote:
           | The popularity of these drugs is specifically from the FDA-
           | approved "weight loss" indication. You're at least a few
           | years behind. I would also think the many many years when it
           | was only prescribed for diabetes would have yielded some data
           | about negative effects, (other than the ocular issue) if
           | there were any. Glp-1s were so unprofitable, Novo Nordisk let
           | their Canadian patent lapse almost a decade ago, rather than
           | pay the upkeep fee lol. So I dont think anyone is protecting
           | them from bad press.
        
         | CyanLite2 wrote:
         | Its not upside per se, more like avoiding the downsides of
         | diabetes and obesity.
         | 
         | Healthy, non-obese individuals likely aren't seeing these
         | "benefits"... But I'm not a doctor, I just pretend to be one on
         | the Internet.
        
           | dillydogg wrote:
           | This isn't true, the heart and kidney benefits appear
           | independent of weight loss. I would encourage you to let the
           | physicians speak to these effects instead of making educated
           | conjecture; it is tough to keep ahead of all of the claims
           | about these medications with my patients.
           | 
           | https://www.science.org/doi/10.1126/science.adn4128
        
         | toomuchtodo wrote:
         | Many Americans drive a car every day, even though ~40k people a
         | year die in car accidents. Why? Because the benefits outweigh
         | the risk.
         | 
         | (my partner is on a GLP-1, and lost ~25 lbs in 3 months)
        
           | culi wrote:
           | > Why? Because the benefits outweigh the risk
           | 
           | Many of us wish we didn't have to drive a car. Many of us
           | also wish we didn't live in a world where hyperprocessed
           | foods weren't the norm
        
             | toomuchtodo wrote:
             | Agreed, but we must operate and decision in the world we
             | live in, not the world we wish we lived in.
        
           | thefz wrote:
           | > Many Americans drive a car every da
           | 
           | Coincidentally also a factor of why many Americans take GLP-1
           | frugs
        
             | chrisco255 wrote:
             | Not really, Americans have been driving cars for over 100
             | years but the obesity epidemic cropped up in the last 30
             | years.
        
               | atherton94027 wrote:
               | Per-capita volume of miles traveled went up by 5x since
               | 1950: https://enotrans.org/article/americans-
               | drove-1-0-percent-mor...
        
               | WithinReason wrote:
               | It's still a factor
        
           | kshahkshah wrote:
           | I'm a huge proponent of GLP's, but with respect to cars I
           | would say that the privatized incentives outweigh the risk to
           | the public
        
         | JumpCrisscross wrote:
         | > _I 'm waiting for the other shoe to drop when it comes to
         | GLP-1s_
         | 
         | We know there are downsides. They're just irrelevant compared
         | to being obese. (Or alcoholic. Or, potentially, overweight.)
         | 
         | It might be a vitamin, where there literally aren't any
         | downsides. I'm sceptical of that. But to the degree there is
         | mass cognitive bias in respect of GLP-1s, it's against them. (I
         | suspect these are sour grapes due to the drugs being
         | unreachable for many.)
         | 
         | My frank concern is we're separating into a social media
         | addicted, unvaccinated and obese population on one hand and a
         | wealthy, insured, disease free and fit one on the other. Those
         | are dangerous class and physical divides to risk becoming
         | heritable (socially, not genetically).
        
           | zemvpferreira wrote:
           | GLP-1's should make you less concerned in that case, they're
           | poised to become extremely affordable very soon. Ending the
           | obesity epidemic will do more to bridge the class divide than
           | anything I can practically imagine. Not to mention the other
           | compulsions these drugs help moderate - alcohol, tobacco,
           | gambling etc. It's my best hope for worldwide quality of life
           | improvement in the next 10 years.
        
             | JumpCrisscross wrote:
             | > _Ending the obesity epidemic will do more to bridge the
             | class divide_
             | 
             | My hope is the "waiting for the other shoe to drop" folks
             | are just expressing sour grapes.
             | 
             | If it runs deeper and merges with the anti-vaxers, we've
             | got a behavioural problem fuelling a class divide. _That_
             | is my fear.
        
               | phil21 wrote:
               | I've thought about this a decent amount.
               | 
               | My opinion has shifted over the years. At first I also
               | thought it was largely just sour grapes re: accessibility
               | and fear of the unknown, but now I'm thinking that a
               | large number of people are going to be so far deep into
               | anti-GLP opinions and hot takes they can't backtrack out
               | of it. Much like political or social beliefs you make
               | into your identity. Too embarrassing to admit you might
               | be wrong.
               | 
               | I know you're alluding to the same thing, it's just
               | interesting to me someone else in the world seems to
               | share these thoughts. I also think it may really
               | delineate a multi-generational class divide that is hard
               | to break.
               | 
               | Or all the folks on GLP-1s will develop some rare form of
               | cancer and die early leaving the world to the so-called
               | haters.
        
         | DharmaPolice wrote:
         | I'm sure there will be negative side effects but the main
         | outcome of these drugs is that you eat less. Many of us have
         | trained ourselves to eat at a frequency and volume way beyond
         | what is really required to keep our body functioning. This
         | leads to weight gain in most people and thus is the focus but
         | even independent of weight there are effects of continuously
         | eating poor quality foods which are unlikely to be good. So I'm
         | not surprised that there are all these miraculous sounding
         | positive side effects to drugs which prevent most people from
         | putting their metabolic system under near constant load.
         | 
         | When the side effects are better understood I suspect for the
         | average person, eating less would be a net benefit to their
         | overall health - _even if they don't lose any weight_.
        
         | coffeebeqn wrote:
         | I'm sure some negative effects will be found but from what I
         | understand lowering your weight outweighs (no pun intended) a
         | lot of possible side effects. Closest thing to a miracle cure
         | and quality of life improvement
        
         | 45764986 wrote:
         | These drugs have been around for more than 10 years. If there
         | were significant downsides, we probably would have seen them
         | already.
        
         | bossyTeacher wrote:
         | Given all the potential money, if they are issues, I expect it
         | to go down like tobacco companies back in the days actively
         | suppressing undesirable research by harassing researchers,
         | influencing peer review journals or/and funding research
         | casting doubt on the benefits of this drug. Chances are that
         | any negative effects won't be obvious until it's too late. Look
         | at microplastics, they have been around for just over a century
         | and it's only now that we are starting to realize that they
         | have several negative effects.
        
           | CoastalCoder wrote:
           | I agree. I think it's _unlikely_ that negative effects can go
           | unnoticed for very long, but in the short term I 'm only like
           | 97% sure we're getting the full story.
           | 
           | That said, it's probably certain enough for me to be open
           | enough to using them now, if my doctor recommends it.
        
         | xtracto wrote:
         | Several members of my family are into glp-1 both for glucose
         | control and for weight loss. Taking different brands (wegovy,
         | ozempic and others.) They all mention.th terrible secondary
         | effects when you eat something "forbidden" (tacos, cake or
         | icecream e.g.) .                 Also It causes constipation
         | apparently,  which for most of them is not that much of an
         | issue, but given that I've IBS-C, I'm happy to not have to take
         | it.
        
           | tssva wrote:
           | I take a glp-1 and suffer no ill effects when I eat something
           | "forbidden".
        
             | icebergonfire wrote:
             | More anecdata, my spouse and I have been on Mounjaro since
             | Jan 2025 guided by private health insurance.
             | 
             | I have suffered almost the entire gamut of side effects
             | from the beginning until I tried split dosing twice a week,
             | and even then there's still the occasional instance of me
             | learning that I should not have eaten _that_ and the
             | following 9 hours are going to revolve around stomach pain.
             | 
             | My partner's journey on the other hand has been smooth
             | sailing the entire time.
             | 
             | YMMV, do your own research but definitely double check any
             | search results with your doctor first... lots of urban
             | myths going around.
             | 
             | I do recommend it though, I am the healthiest I've been in
             | literally 10 years.
        
           | CoastalCoder wrote:
           | I'm surprised that tacos are a big deal. I'd have thought
           | that the filling (meat, cheese, veggies, maybe beans) would
           | mostly outweigh the carbs from the shell.
        
         | m463 wrote:
         | I wonder if you could ask: are there downsides to losing
         | weight?
        
           | MangoToupe wrote:
           | Hey some of us struggle to eat enough and/or remember to eat
           | in the first place
        
         | PeaceTed wrote:
         | I am sort of in your boat in seeing what may come. There are a
         | few very rare conditions but the benefits seem to out weigh
         | (ha, I will take the pun!) The down sides.
         | 
         | While it might mean the incident rare of some things goes up,
         | those that it reduces are far more impactful and where far more
         | likely to have mortality issues. Sort of like how Chemotherapy
         | is poisonous but potential has better long term odds, only
         | chemo is far more extreme than GPL1.
         | 
         | Time will tell but so far it is looking kind of good with a few
         | lesser issues.
        
           | CoastalCoder wrote:
           | > chemo is far more extreme than GPL1.
           | 
           | Which is ironic because someone at Microsoft once called the
           | GPL "cancer".
        
         | thefz wrote:
         | > Maybe I'm just an aging cynic, but I'm waiting for the other
         | shoe to drop when it comes to GLP-1s. There have been so many
         | claims of positive benefits that it almost seems too good to be
         | true.
         | 
         | Well, read up the testimony of those who stopped taking it for
         | adverse effects, such as nonexistent intestinal transit and
         | -yuck- sulfur burps.
        
         | 01100011 wrote:
         | I was in that boat too but with NAFLD and now liver fibrosis
         | despite not eating all that much sugar and having a BMI that is
         | high but partially due to muscle I finally gave in to see if
         | semaglutide will help.
         | 
         | Only on week 3 but it's been a rollercoaster. It seems to have
         | quite a broad spectrum of effects. I'm still not sure I'll be
         | able to stay on it but losing 10 pounds is a nice counterpoint
         | to the side-effects.
        
         | mannanj wrote:
         | Right. This is what we heard about the COVID therapies. And we
         | all know how that turned out to be little more effective than
         | placebo for healthy non-comorbid people.
        
         | glp1guide wrote:
         | Basically, the gastro-intestinal side effects are the biggest
         | issue, along with CVS (not the store) and possibly eye
         | problems.
         | 
         | That said, the negative side effects look to be incredibly rare
         | and manageable (including via stopping treatment) -- and the
         | positives are quite tremendous.
         | 
         | It's not a magic drug, but it is the first of it's kind with
         | such a skew to the positive on side effects.
        
           | brazukadev wrote:
           | > It's not a magic drug
           | 
           | It actually is a magic drug. The same way ultra-palatable
           | food is also not natural.
        
         | Der_Einzige wrote:
         | This kind of "it's too good so it must be bad" thinking is a
         | cancer in our species.
        
           | hollerith wrote:
           | I agree. A better response is, "maybe GLP-1 drugs are really
           | great or maybe the drug companies, which spend most of their
           | time and money trying to manipulate opinion (i.e., by bribing
           | researchers and clinicians, which is not illegal) are at it
           | again."
        
       | agentifysh wrote:
       | is there an extract or can you get it from natural food? which
       | have it ?
        
         | phantasmish wrote:
         | GLP-1 agonists? Well they derived them from a lizard, so, uh...
         | sort of? But no, no foods you eat are really going to have
         | GLP-1 agonists in them, not to any meaningful degree anyway.
         | Plus if you're eating them they have to survive at least part
         | of the digestive tract, which means you need even more since
         | some of it'll be lost.
         | 
         | Your body produces GLP-1, but it lives in the blood for like
         | minutes. The innovation was finding a chemical that tickles the
         | same receptors but survives in the body for days at a time.
        
         | cstrahan wrote:
         | There may be some herbal supplements that impact GLP-1 release
         | to some extent, but what is being talked about here are
         | synthetic GLP-1 receptor agonists.
        
         | mrtesthah wrote:
         | https://www.sciencedirect.com/science/article/pii/S221112471...
         | 
         | L-tryptophan > Indole > Raises GLP-1
        
         | fleetwood wrote:
         | Resistant starch
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC10085630/
         | https://pmc.ncbi.nlm.nih.gov/articles/PMC4030412/
        
       | ck2 wrote:
       | no GLP-1 generics until 2030
       | 
       | lots of people will miss out on benefits, like oh preventing
       | death
       | 
       | our drug system is weird
        
         | exabrial wrote:
         | Private people invested a lot of money to develop this and get
         | it through testing. Allowing them to reap the benefits from
         | their investment for a limited time is just fine.
         | 
         | It's not people couldn't also: Diet, exercise, choose veggies,
         | eat more fiber, etc
        
           | isoprophlex wrote:
           | "Sorry bro gonna let you die because, muh investments, you
           | see"
           | 
           | Your closing remark is overly simplistic and offers a
           | contradiction: if those things would work for these obese
           | people, they wouldn't need GLPs.
        
             | exabrial wrote:
             | The laws of thermodynamics apply to everyone equally.
        
               | asdff wrote:
               | Where in thermodynamic principles does it suggest money
               | ought to flow into the pockets of the few?
        
               | phantasmish wrote:
               | The standard for medical interventions usually isn't
               | "could it work?" or "should it work?" but "does it work?"
               | 
               | This is why the efficacy of every single contraceptive
               | method isn't way higher than it is. Lots of them _should_
               | work almost perfectly... but the harder they are to use
               | correctly, the less effective they in-fact are.
        
               | exabrial wrote:
               | Eating less, exercising more, has worked for the entire
               | existence of human race. In fact, it worked for me just
               | fine too. GLP-1s are a safe and proven tool and should be
               | used wherever appropriate to assist people. Both of these
               | are simple facts that aren't in contradiction with either
               | other.
               | 
               | But saying the patent owners shouldn't be allowed to reap
               | the benefits of their investment is ridiculous,
               | especially when it's completely possible to lose weight
               | in other ways. 6 years isn't that long to wait anyway.
        
             | ck2 wrote:
             | just want to point out it's not just for obesity
             | 
             | GLP-1 has been demonstrated to even cure some types of
             | long-covid in some people in some cases
             | 
             | and various other diseases
             | 
             | but it's priced way out of reach even for micro-doses until
             | it becomes generic
             | 
             | so all those cases suffer until 2030, if they make it that
             | far, five years is a long time
        
           | asdff wrote:
           | The public also invested a lot of money.
        
           | cess11 wrote:
           | Kind of weird to assume other people think it's fine to
           | exchange human lives for money.
           | 
           | Is it ethical for me to pay someone to murder you? Does it
           | matter if it costs me a large amount of money or not?
        
             | exabrial wrote:
             | This is a great example of a straw-man attack.
        
               | cess11 wrote:
               | No, it is not. They said that since someone, which is
               | typically a fictive person, had spent a lot of money,
               | they deserve to restrict physical persons' access to
               | supposedly life saving substances.
               | 
               | I would like to know how far they take that position.
        
               | WillPostForFood wrote:
               | How many people do you feel liek you are personally
               | responsible for killing because you haven't given 100% of
               | your disposal income to food relief? Hundreds? Thousands?
        
               | CobrastanJorji wrote:
               | This isn't "I could use my money to acquire food for the
               | poor." It's "I'm going to prevent anyone else from
               | selling food, and that will let me charge 100x as much
               | for food."
        
             | ashdksnndck wrote:
             | Why do we pay doctors? Are they evil if they refuse to go
             | to work for free?
        
           | k_roy wrote:
           | Protecting it before generic is fine, but the pricing doesn't
           | make sense.
           | 
           | If it's $1000 per month cost per person when it's the name
           | brand, how many people are on it? At this point just the
           | diabetics and people with really good insurance?
           | 
           | Wouldn't they make a hell of a lot more money selling it for
           | $100 during their protected period to 1000x the people.
        
             | kube-system wrote:
             | They have direct discount programs where they sell at ~
             | half price.
        
               | pretzellogician wrote:
               | True, but also still absurdly high. Novo Nordisk and Eli
               | Lilly cost roughly $500 monthly... but the price is
               | almost the same regardless of the dosage (from say 0.5mg
               | to 2.4mg).
        
           | MangoToupe wrote:
           | > Allowing them to reap the benefits from their investment
           | for a limited time is just fine.
           | 
           | Or we could just move to a sane economic system where we
           | don't have to beg the rich/reward people for having money
        
           | km144 wrote:
           | Those things also require more willpower than taking a
           | medication. Willpower is generally determined by your
           | particular psychology which is determined by genetics and
           | environmental factors. People don't have a choice in the
           | matter as much as your comment seems to imply. Getting GLP-1s
           | to everyone who could benefit from them is extremely
           | important for overall health.
        
         | mrtesthah wrote:
         | In theory you could supplement with L-tryptophan which is
         | metabolized into indole which then raises GLP-1 production
         | within enteroendocrine cells.
         | 
         | https://www.sciencedirect.com/science/article/pii/S221112471...
        
           | matthewdgreen wrote:
           | Or anything that boosts Akkermanskia.
        
           | Bender wrote:
           | I use that to help me stay asleep. I also feed large amounts
           | of it to horses and deer before, during and after 4th of July
           | since everyone here launches mortars from their fields. Helps
           | them chill.
        
           | degamad wrote:
           | It's not obvious that there is a benefit here - the third
           | sentence of the summary at the top says:
           | 
           | > Indole increased GLP-1 release during short exposures, but
           | it reduced secretion over longer periods.
        
         | kube-system wrote:
         | Compounded GLP-1s are still floating around in the US
        
           | ck2 wrote:
           | if you saw the 60 Minutes on compounding pharmacies, which
           | are completely unregulated and never inspected, and sometimes
           | contaminate products out of lack of care/repercussions
           | 
           | you'd never touch a compounded pharmacy product ever again
           | 
           | people have died from contamination
        
             | kube-system wrote:
             | Compounding pharmacies are regulated by section 503 of the
             | FD&C act, and also subject to inspection.
             | 
             | Are you referring to the fact that the FDA does not inspect
             | all facilities because they have limited resources? This
             | applies to pharmaceutical companies as much as it does to
             | compounders. If you think the FDA posts inspectors at every
             | pharmaceutical company in India, you'd be wrong.
        
             | ACCount37 wrote:
             | People are straight up buying black market "research use
             | only, not to be used in humans" GLP-1. Compounding
             | pharmacies are reliable, safe and well regulated compared
             | to that.
             | 
             | Clearly, there's an entire spectrum of tradeoffs between
             | safety/shadiness, availability and price. I think that's a
             | good thing.
        
           | kshahkshah wrote:
           | I compound tirz with glycine and B12. I honestly think these
           | are miracle drugs.
           | 
           | I've never been extremely overweight but I hit a point where
           | I had 30 pounds to lose, despite my height, and I can't deal
           | with the hunger amidst all my other life stresses.
        
         | pretzellogician wrote:
         | There are already GLP-1 generics available like liraglutide;
         | they're just not as effective as the newer ones.
         | 
         | (This refers to the U.S. Some other countries have more
         | generics available.)
        
         | glp1guide wrote:
         | Like others have mentioned, liraglutide already exists as a
         | generic! It's not as good as Semaglutide or Tirzepatide, but.
         | 
         | Also, a lot of people are still getting compounded GLP1, to the
         | chagrin of Eli Lilly and Novo Nordisk.
         | 
         | Separately, 2026 is about to completely change the pricing of
         | this stuff, not even taking into account the Trump
         | administration's recent efforts. The price of injected GLP1 is
         | going to implode due to patents lapsing in Canada and other
         | places -- and for the pill forms that come out soon it looks
         | like the Trump administration is keen on keeping prices for
         | that low as well.
        
       | jl6 wrote:
       | > However, the study authors emphasize that more research is
       | needed to confirm these mechanisms and determine whether the
       | survival benefit observed in this real-world analysis represents
       | a direct anti-cancer effect or an indirect result of improved
       | metabolic health
       | 
       | Given it's an observational study, I would bet on the latter.
       | It's really hard to know you've controlled for all confounding
       | factors, and there's a strong null hypothesis because we know
       | that losing weight can have huge and wide-ranging health
       | benefits.
        
         | stavros wrote:
         | Yeah, most GLP-1 benefits (or even adverse effects, like muscle
         | loss) seem to be caused by the weight loss. We already knew
         | obesity massively increases risk from a host of diseases, but
         | GLP-1s are still treated with scepticism of the "oh but what
         | about the side-effects we don't know about?!" variety?
        
           | ed wrote:
           | Source?
           | 
           | There's growing evidence of cardioprotective effects
           | independent of weight loss.
           | 
           | Eg https://www.thelancet.com/journals/lancet/article/PIIS0140
           | -6...
           | 
           | > The cardioprotective effects of semaglutide were
           | independent of baseline adiposity and weight loss and had
           | only a small association with waist circumference, suggesting
           | some mechanisms for benefit beyond adiposity reduction.
        
             | rickydroll wrote:
             | They also help with slowing the progression of CKD
             | 
             | https://www.kidneyfund.org/treatments/medicines-kidney-
             | disea...
        
           | anovikov wrote:
           | Someone has to start a study where they give GLP-1 to skinny
           | people and see what happens. Why it hasn't been done yet?
        
             | stavros wrote:
             | Because they lose weight and it's too dangerous.
        
               | anovikov wrote:
               | They won't, GLP-1 has almost no direct effect on skinny
               | people. Many women with BMI around 22-23 are trying them
               | to lose weight to match beauty standards and usually end
               | up disappointed, not able to drop more than 1-2 kilos.
        
         | cyrusradfar wrote:
         | Agreed.
         | 
         | I'm a big fan of intermittent and water fasting. Have seen
         | things in my blood work that doctors would require me on meds
         | to reverse. Outside of that, I can't speak to the positive
         | impacts on my mood, and general ability to focus.
         | 
         | The simplest solution to a lot of problems is consuming less
         | with the assumption that, most of us (maybe not you), have a
         | lot of spare energy sitting around.
         | 
         | A lie that we don't unlearn as we grow up is we "require" three
         | meals a day. This is true for children who need obscene amounts
         | of energy to grow, but, not for us desk-bound adults.
         | 
         | In the end, giving the body a break to heal by fasting or just
         | consuming significantly less is going to leave more resources
         | for the body energy to deal with other things.
        
           | trallnag wrote:
           | Awesome insight. It's not the disability I have, it's that I
           | have never tried healing by fasting. Of course. Because my
           | body was always busy trying to eat food instead of fixing and
           | regrowing all the malformed tissue. Because that's how it
           | works. When a person without legs starts to fast, the legs
           | will suddenly develop.
        
             | amenhotep wrote:
             | It would be sensible for you to examine and interrogate why
             | reading a general and fairly anodyne opinion about what
             | might be a solution to a problem some people have led you
             | to interpret it as a prescriptive and judgemental
             | suggestion about the specific problem you specifically
             | have.
        
               | cyrusradfar wrote:
               | Appreciate the thoughtful retort. Have a good one.
        
               | trallnag wrote:
               | In my mind it is a slippery slope that leads to a sickly
               | Steve Jobs eating kilograms of raw carrots.
               | 
               | Obviously a healthy lifestyle is good. And this includes
               | not eating over your requirements. But sometimes there is
               | actually something wrong. And in these cases, first
               | trying out to just eat healthy can worsen the situation
               | by delaying proper treatment. And proper treatment does
               | equal a bunch of pharmaceutical drugs.
        
               | mock-possum wrote:
               | I disagree, I think it's fairly easy to read this passage
               | in particular
               | 
               | > The simplest solution to a lot of problems is consuming
               | less with the assumption that, most of us (maybe not
               | you), have a lot of spare energy sitting around.
               | 
               | as energy-woo / thanks-I'm-cured material.
               | 
               | You can weasel your way around criticism by calling it "a
               | general and fairly anodyne opinion about what might be a
               | solution to a problem some people have," but consider -
               | 
               | It does make sense that someone who's struggled with a
               | chronic condition would be tired and embittered by the
               | endless snake oil evangelizing they've had to endure, _on
               | top of_ already struggling with their health.
               | 
               | (Not that fasting doesn't work for some people, as you
               | say! it's more the grandiose claim that it's "The
               | simplest solution to a lot of problems" coupled with some
               | vague anecdote about blood work and knowing better than
               | doctors that waves a red flag)
        
           | itchyouch wrote:
           | An interesting FYI is a comment made by Peter Attia on his
           | podcast.
           | 
           | He had a patient with metabolic markers that were not
           | improving and they had exhausted all the typical avenues.
           | Presumably they were things like weight loss.
           | 
           | They put the patient on GLP-1 but injected into the thighs
           | (or butt, I don't recall) for the metabolic benefits without
           | the hunger blunting effects.
           | 
           | It seems like GLP1, even in skinny patients (implied by Attia
           | in this particular case), has metabolic benefits.
           | 
           | The longevity community seems to be hinting that there may be
           | geroprotective aspects of GLp1 as well, so we may be looking
           | at the benefits beyond weight loss for metabolism.
        
             | asmor wrote:
             | (Outer) Thigh, upper arms and stomach are the on-label
             | injection sites for these drugs.
        
             | ifwinterco wrote:
             | It shouldn't make any difference where you pin it, it's
             | systemic it just has to be administered subcutaneously
             | because it's a peptide and it isn't orally active.
             | 
             | Don't listen to these YouTubers about health and fitness,
             | most of them are clueless
        
               | avgDev wrote:
               | Pseudoscience scares me. There are so many people that
               | believe this nonsense and basic understanding of medicine
               | disproves many of those claims.
        
               | op00to wrote:
               | It shouldn't, and yet for me it seems to make a
               | difference! I don't think it's placebo, because I am
               | really losing weight. My anecdata: When I start with a
               | particular dose of GLP-1, I inject in thigh. I get strong
               | appetite suppression, heart rate increase, digestion slow
               | down etc. After some time, the effect decreases as my
               | body adjusts. I then move injection to abdomen, and I get
               | a huge bump in suppression, systemic effects, etc. No
               | idea why this happens, but I've seen it with Zepbound and
               | 5, 7.5, and 10mg. It's allowed me to stay on each dose
               | for far longer than my doctor expected.
        
               | itchyouch wrote:
               | There were no recommendations.
               | 
               | Usually this type of anecdata becomes the basis of
               | legitimate, controlled studies and over time can inform
               | and/or adjust.
               | 
               | It would be premature to simply write off all influencers
               | or limiting to only accept the medical profession as the
               | immutable truth.
               | 
               | The reality tends to exist somewhere in the middle,
               | outside of a formal proof.
               | 
               | I've listened to many health influencers and among the
               | legitimate and balanced tend to be Rhonda Patrick and
               | Peter Attia.
               | 
               | Attia provides guidelines for how to think about items,
               | but usually it's the fan base that tends to sully the
               | messaging as the base tends to be far more polarized and
               | dogmatic over bits.
               | 
               | It is interesting to see that there is another poster
               | confirming a slightly different effect though. Regardless
               | of things being "systemic", just understanding that
               | fluids dynamics are complex, I imagine diffusion of a
               | systemic molecule like GLp1 could possibly be variable?
               | Or perhaps there is a localized tissue fatigue?
               | 
               | Many potential options do exist to propose as hypothesis.
        
               | itchyouch wrote:
               | While the area under the curve for glp1 administration
               | may be the same, good chance that the story is informing
               | us of a mechanism such as the absorption rate between two
               | different sites.
               | 
               | Slower absorption in the thigh may blunt the immediate
               | peak dosing and the acute hunger effects.
               | 
               | As always, the small details matter. I'd guess that
               | pharmacology also has their own thundering herd problem
               | with the dosing of certain drugs.
               | 
               | One of the interesting bits about pharmacology seems to
               | not be the active molecule as much as the innovations in
               | delivery mechanism.
        
             | gavinray wrote:
             | > They put the patient on GLP-1 but injected into the
             | thighs (or butt, I don't recall) for the metabolic benefits
             | without the hunger blunting effects.
             | 
             | Thanks for the dumbest thing I've read all day
        
           | l5870uoo9y wrote:
           | There is no such thing as water fasting. I would characterize
           | it as an eating disorder.
        
             | cyrusradfar wrote:
             | Umm.
             | 
             | Sources?                 -
             | https://en.wikipedia.org/wiki/Fasting       -
             | https://zerolongevity.com/blog/the-history-of-fasting/
        
             | InMice wrote:
             | Of course. That's why the nobel prize in medicine in 2016
             | was awarded to a cell biolgoist studying cellular autophagy
             | for over a decade. It must be why glucose is not an
             | essential dietary macronutrient and our liver can
             | synthesizie it endogenously from fats and proteins (it just
             | felt like doing that one day and stored all those chemical
             | pathways in our genes I guess). That must also be why
             | ketones produced from our fat stores burn so cleanly with
             | less reactive inflammatory byproducts. In fact the cells in
             | our brain actually prefer ketones to glucose. There's no
             | such as water fasting. It's just random chance that when
             | the body is in a state of ketosis it suppresses ghrelen and
             | other hunger hormones or that countless other chemical
             | pathways (de)activate or change. That's right the body has
             | absolutely no design or adaptation for scarcity of food.
             | Water fasting is totally foreign to the human body, that's
             | why whenever we study ancient cultures...we find they
             | practiced purposeful fasting. There's just no such thing as
             | water fasting, it must be a modern eating disorder.
             | 
             | There's no chance it has anything to do with the last few
             | million years of our evolution. It has no benefit or
             | relevance now.
        
               | l5870uoo9y wrote:
               | Took "water fasting" to mean fasting even without water,
               | apparently it is the opposite.
        
               | InMice wrote:
               | LOL total misunderstanding then. No problem.
        
           | Cthulhu_ wrote:
           | I for one don't "require" three meals a day, but I'm hungry
           | in the morning, ergo, I like breakfast.
           | 
           | It's not so much about how often you eat but what and how
           | much. Generally speaking, of course, I can't speak for any
           | benefits of intermittent fasting (assuming equal daily
           | calorie / macronutrient intake) because I'm uneducated in
           | that regard. But TL;DR, I will agree that desk jockeys will
           | need less calories than people with a more active job or
           | lifestyle, and people need to adjust their lifestyle
           | accordingly else they'll gain weight.
        
             | foobarian wrote:
             | Maybe this goes away after a while, but when I tried this
             | in the past I get so hungry I can't think or work. So
             | clearly it's a non-starter for me on work days.
        
               | codr7 wrote:
               | It takes time to get used to the feeling, to accept that
               | it's not dangerous, quite the opposite.
               | 
               | Also the body gets used to not being full all the time,
               | it will stop signalling so hard.
               | 
               | Try it in the weekends first? Once you start enjoying the
               | feeling, and you will, it will happen by itself.
        
             | codr7 wrote:
             | Yeah, the problem with mornings is that it's probably the
             | worst time of day to eat.
             | 
             | Because the body flushes all stored up energy when you wake
             | up, likely an evolutionary adaptation as breakfast was
             | rarely served on a silver plate.
        
           | InMice wrote:
           | ALmost everyone who shares their positive, any length fasting
           | experience here gets downvoted. I will always upvote them.
           | Ive done two 48 hour fasts and they were so relaxing and felt
           | so natural. It just feels great to occasionally go about your
           | day and not eat anything. Your gut tries to heal itself in
           | between meals. The fact that almost all of HN just cant stand
           | anyone mention they fast with positive benefits (and mounting
           | evidence) is kidna sad. I guess every community has to be
           | exceptionally closed minded about something.
        
             | lazyasciiart wrote:
             | If you include as much meta-commentary every time, you're
             | certainly going to get downvoted.
        
           | codr7 wrote:
           | Yeah, it's been a gradual process for me, feeling comfortable
           | with being hungry.
           | 
           | But the less I eat, the better my health gets; I'm down to
           | one normal sized meal per day, have been doing that for
           | months.
        
         | p00dles wrote:
         | Interesting that GLP-1s might have different effects on cancer
         | _incidence_ vs. cancer _survival_.
         | 
         | A different study "GLP-1 Receptor Agonists and the Risk of
         | Thyroid Cancer" was published in the Diabates Care journal in
         | February 2023*
         | 
         | The conclusion of the 2023 study: "we found increased risk of
         | all thyroid cancer and medullary thyroid cancer with use of
         | GLP-1 RA, in particular after 1-3 years of treatment."
         | 
         | I wonder what the mechanistic hypothesis could be for GLP-1s
         | increasing thyroid cancer _incidence_ (the probability of
         | thyroid cancer occurring in patients taking GLP-1s) but
         | increasing colon cancer _survival_ (the probability of
         | surviving in patients taking GLP-1s who have colon cancer).
         | 
         | Of course there are numerous important differences across the
         | studies (cancer type, France vs. USA data, etc.), I'm just
         | curious about a why this might be the case.
         | 
         | *https://diabetesjournals.org/care/article-
         | abstract/46/2/384/...
        
           | mr_luc wrote:
           | I'd be cautious for the same reason: thyroid cancers are also
           | positively associated with obesity, and people who take
           | GLP-1s are often obese.
           | 
           | Below a table, it says "adjusted for social deprivation
           | index, hypo- and hyperthyroidism, and use of other
           | antidiabetic drugs..." -- but nothing about obesity.
           | 
           | What if the GLP-1-prescribed patients tended to be more
           | obese?
        
         | freetime2 wrote:
         | The article also says that the effects persist after adjusting
         | for BMI:
         | 
         | > After adjusting for age, body mass index (BMI), disease
         | severity and other health factors, GLP-1 users still showed
         | significantly lower odds of death, suggesting a strong and
         | independent protective effect.
         | 
         | The observed reduction in mortality is also quite large:
         | 
         | > Health sites, researchers found that those taking glucagon-
         | like peptide-1 (GLP-1) medications were less than half as
         | likely to die within five years compared to those who weren't
         | on the drugs (15.5% vs. 37.1%).
         | 
         | More research is needed, but if I were diagnosed with colon
         | cancer I would definitely be asking my doctor about the risks
         | vs. potential benefits of getting on GLP-1 meds based on this
         | study alone.
        
       | andy_ppp wrote:
       | If you eat less your stomach/whole body gets time to relax and
       | repair?
        
         | pedalpete wrote:
         | My understanding is that it slows the digestive process, so
         | there isn't more "empty time to repair or relax".
         | 
         | But my thinking there may be naive.
        
           | andy_ppp wrote:
           | I just know someone who skips breakfast and lunch on the
           | jabs... maybe he eats dinner I've not checked.
        
             | icebergonfire wrote:
             | Anecdotally speaking I can confirm this... it gets easy to
             | _just_ skip a meal, and you may end up skipping the entire
             | day because the usual hunger signals are just not there.
             | 
             | For anyone tempted by that concept, please don't and
             | remember to try to eat your 1000-1500 calories every day.
             | 
             | Quick weight loss won't do you any good if you lose all
             | your muscle mass, or if you carve a deeper groove into body
             | image issues.
             | 
             | It's cliche but it's true, slow and steady is the way to
             | go.
        
           | glp1guide wrote:
           | At this point most experts lean more heavily on the effect of
           | GLP1s in the brain rather than delayed gastric emptying --
           | it's more of a brain drug than anything else which is why it
           | works so well.
        
       | Noaidi wrote:
       | I do not like the framing. GLP-1 drugs help people lose weight,
       | and it is the weight loss that lowers death rates in colon
       | cancer[1]. This is making it sound like the drug itself is
       | reducing cancer.
       | 
       | [1] https://link.springer.com/article/10.1007/s12672-025-03902-4
        
         | surfsvammel wrote:
         | I don't agree. They are not saying that.
         | 
         | It's observational. They are saying they see correlation.
         | 
         | Your suggested mechanism is plausible, and likely, of course,
         | but that might only be part of the effect.
         | 
         | I think it's still valuable findings and can help direct
         | further studies.
        
       | surfsvammel wrote:
       | I am on GLP-1 (very low dose), and I've found that it seems to
       | help me moderate my alcohol consumption as well. Maybe some thing
       | like that could also be contributing to the effect.
        
         | richwater wrote:
         | Is there evidence for addiction tendencies in general? Or is it
         | something specific to alcohol?
        
           | surfsvammel wrote:
           | I don't know! Think I've seen a headline somewhere, but can't
           | remember where. Quick search should help you :)
           | 
           | To me, it's anecdotal, of course, but I have same sense of
           | being in control over alcohol intake as food intake.
           | 
           | Basically makes it much easier for me to avoid binging.
        
           | zemvpferreira wrote:
           | I'm about to go to the cinema so I can't find you references,
           | but there's a lot of anecdotal evidence at least of glp1's
           | curbing all sorts of addictive behaviour. I personally
           | started Mounjaro last week and my coffee cravings have gone
           | way, way down for the first time in my adult life.
        
           | SoftTalker wrote:
           | I believe there is, I don't recall the source but have read
           | that these drugs work by reducing cravings. So they have
           | shown at least hints that they can work on any addictive
           | behavior, not just overeating.
        
           | toomuchtodo wrote:
           | _A Brain Reward Circuit Inhibited By Next-Generation Weight
           | Loss Drugs_ - https://www.biorxiv.org/content/10.1101/2024.12
           | .12.628169v1.... | https://doi.org/10.1101/2024.12.12.628169
           | - December 17rd, 2024
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           |  _Glucagon-like peptide 1 agonist and effects on reward
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           | https://doi.org/10.1016/j.physbeh.2024.114622 - Physiology &
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           |  _GLP-1 for Addiction: the Medical Evidence for Opioid,
           | Nicotine, and Alcohol Use Disorder_ -
           | https://recursiveadaptation.com/p/the-growing-scientific-
           | cas... - May 14th, 2024
           | 
           |  _The central GLP-1: implications for food and drug reward_ -
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           | Neurosci., October 13th, 2013
        
           | CobrastanJorji wrote:
           | From my friends on GLP-1s, I'm pretty sure that it's mostly
           | that it makes you really sick fairly quickly when you drink
           | even in moderation.
        
         | donsupreme wrote:
         | I hypothesize that the appetite-suppressing effect of GLP-1
         | agonists contributes to the normalization of dopamine signaling
         | in the brain. By mitigating the exaggerated dopamine
         | fluctuations seen in food and sugar addiction, GLP-1 may
         | promote a return to dopamine homeostasis, thereby reducing
         | compulsive or addiction-like reward-seeking behaviors.
        
           | foobarian wrote:
           | Wonder if it would help compulsive gamblers then.
        
             | basisword wrote:
             | I think that's already been shown (at the very least I've
             | read news articles with anecdotes).
        
         | fgimenez wrote:
         | They have a lot of anecdotal, observational, and emerging RCT
         | evidence on their effects on substance consumption and abuse.
         | 
         | The biggest effect and best tested is on alcohol use disorder.
         | Mechanistically we don't know if it's through some complex
         | reward mechanism, or something simpler like "alcohol is a
         | calorie and you consume fewer calories." The JAMA study showed
         | that GLP-1 reduce Heavy Drinking Days (>2 drinks/day), but did
         | not reduce overall drinking days. This would imply the simple
         | mechanism -> it's hard to drink a lot of calories even if you
         | do enjoy a drink.
         | 
         | More anecdotal evidence showing this effect in opiates, but
         | nothing in an RCT yet.
         | 
         | So far, nothing has worked in stimulants. Cocaine and Meth
         | abuse are insanely difficult to manage therapeutically right
         | now.
        
         | hexbin010 wrote:
         | Same here. There's less wanting it but also, if I do indulge
         | even one small glass of wine, the side effects are awful:
         | broken sleep, acid reflux and a hangover the next day. It
         | really slaps you in the face for indulging
        
           | Cthulhu_ wrote:
           | Harsher side-effects to drinking sounds like an effective
           | deterrent (although you'd think people would quit after that
           | one hangover they'll never forget). Works for me with candy,
           | a lot of it gives me tooth pain. My teeth are otherwise
           | healthy, no cavities or anything.
        
         | aswegs8 wrote:
         | Does the very low dose help with weight management?
        
           | pretzellogician wrote:
           | It depends on the person, but for some (including me) a low
           | dose is enough.
           | 
           | Conversely, for some (including me) a moderate dose has
           | intolerable side effects.
        
         | _1 wrote:
         | Same. two drinks and I'm done
        
       | basisword wrote:
       | I am 100% a layman here so apologies if this is a stupid
       | analysis. But I have read that fasting can improve odds and
       | improve side effects during chemo. Would GLP-1 stabilising blood
       | sugar be having the same effect?
        
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