9 ms·

Is there any good consensus on what the deal is with this drug yet? I don't know how to think about GLP-1. In the headlines it seems like every month it's a mir

• michaelbuckbee 11mo ago
  I agree with you. All I can think is that it's affecting some central mental or physical aspect that has many different outward benefits.
  • toomuchtodo 11mo ago
    It patches the reward center in the brain, which improves everything downstream of that (as mentioned in llm_nerd's sibling comment to yours). https://news.ycombinator.com/item?id=45907422 https://news.ycombinator.com/item?id=45907422 (citations) (i am hopefully that probiotics might be a future path to curating gut microbiota that meets an individual's GLP-1 in vivo production needs based on target metabolic outcome, but immediate intervention is welcome for obvious health reasons at scale)
• llm_nerd 11mo ago
  GLP-1 is a naturally occurring hormone regulating blood sugar, satiety, and gastric emptying. Some people simply don't have enough naturally (which can be a result of diet composition and lifestyle -- there are diet and behaviour modifications to increase your natural production) and artificial supplementation is beneficial. The overwhelming benefits from GLP-1 are courtesy of weight loss and better blood sugar control. Get those two things under control, with or without GLP-1 drugs, and an enormous array of complications are made less likely. For people with healthy, ideal diets at an optimal weight and with good blood sugar control, there are only remote, hypothetical benefits. There is some evidence it reduces inflammation and might ward off neurodegenerative disorders, but those likely have more of a relationship with blood sugar spikes, and again lifestyle changes are more impactful.
  • borski 11mo ago
    This is absolutely correct. I couldn’t have said it better myself. (Except I’ll note that’s true for more than one hormone, as tirzepatide is both a GLP1 and GIP agonist, and I believe retatrutide is also Glucagon?)
    • barrenko 11mo ago
      "Incretins" is the keyword here.
      • borski 11mo ago
        Indeed! Thank you!
  • snarf21 11mo ago
    I agree with most of what you are saying but we should also be clear that there some sources of inflammation that are not caused (or fixed) by diet and lifestyle. There is huge upside for some serious chronic conditions that may be helped by GLP-1 but we are still early on in studies for these things.
  • throwaway2037 11mo ago
    I need to ask: What is it with HN attracting the "inflammation explains everything" crowd whenever there is a discussion about medical topics? I don't understand it. Is there any hard science behind all these explanations of phenom via the inflammation pathway? Or is this just another seed oil conspiracy theory?
    • llm_nerd 11mo ago
      Why in the world did you post this in reply to my comment? Obviously you have some weird hangup, and the fact that I mentioned inflammation quite literally in passing triggered you. Yes, inflammation is a thing in the medical world. There are actual tests to measure it. Having higher levels is generally considered a negative indicator.
• mikhailt 11mo ago
  Nobody understands why it all helps, they just noticed it does work for something, quickly pushed it to the market first to get patents and get all the profits from it before generics + derivatives hit their pockets. Now, everyone is studying it because there's all new funding coming in for it and finding other versions of it that they can profit off it. Nobody knows what migraine really is, so this isn't a surprise to them that GLP-1 may help, the main question is; why? So they have another data point proving that gut health has a direct correlation to the brain. Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects. It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives.
  • borski 11mo ago
    > Keep in mind that a lot of the benefits go away once patients come off GLP-1 and we have not seen any studies yet on what happens to people who come off it for long term effects. Not if they increase muscle mass and change their lifestyle, like every physician (and the FDA/pharma companies) recommend. > It may in fact make things even worse and for a lot of people, they may have to stay on it for the rest of their lives. It does not. And some people may. You know what’s worse than taking a GLP-1 forever? Obesity or metabolic syndrome killing you before you get to “forever.”
    • apple4ever 11mo ago
      > You know what’s worse than taking a GLP-1 forever? Obesity or metabolic syndrome killing you before you get to “forever.” Bingo. Being obese has so many downstream effects. Anything that helps that is tremendous.
      • deleted 11mo ago
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• borski 11mo ago
  It seems weird because we hate finding “bugs” in our bodies, but it happens all the time. Another example: low dose metformin is largely considered beneficial for most people, at least in a small way. But very few people who aren’t diabetic take it, as the drawback of possible side effects outweighs the potential benefit for someone who doesn’t have symptoms in the first place. Same thing here. Would it benefit you? Possibly. Do the risks of side effects outweigh that benefit for someone without symptoms? Also possibly.
  • pfdietz 11mo ago
    Metformin's side effects are pretty minor, I find. So don't let that possibility stop you if you think you could benefit.
    • borski 11mo ago
      I agree with you. My point was simply that most physicians only prescribe if the potential benefits are obvious and outweigh the potential risks / side effects. Doing nothing is something better than doing something without an obvious benefit. If you’re obese, have metabolic syndrome, have T2D, or any other number of issues that we’ve seen GLP-1s (or metformin) help with - then the medications can be a godsend.
• zug_zug 11mo ago
  Yeah... I think part of it is definitely that the profit margin is so high that there's a huge financial incentive to try to make buzz around it before all the patents expire. I guess we'll know for sure when it's available for pennies on the dollar if the buzz continues.
• cjbgkagh 11mo ago
  It’s miracle drug, I’ve been on it for a few years now, it would have been sooner but usage data wasn’t available at the scale I needed before the ozempic craze. I have hEDS and part of that is ME/CFS and uncontrollable weight gain, so naturally I was looking for help with weight loss with the understanding that drugs that help with weight loss could be treating an underlying mechanisms that was causing the weight gain. Low Dose Naltrexone is another drug that also helps with weight loss and hEDS, so I was looking for more of the same. I still don’t know the underlying mechanisms but my autoimmune conditions have largely been resolved. Like cheap solar electricity, I see GLP1s as basically an absolute win. Of course people shouldn’t abuse the drug and they should also change their habits.
  • throwfish3000 11mo ago
    Does having uncontrollable weight gain help you get jacked? Being jacked and fat is tons of fun, better than being skinny.
    • cjbgkagh 11mo ago
      No, it's the worst, just fat but also because I was dieting so much I couldn't tell if I was tired from not eating enough or if I had ME/CFS. After I gained the weight people would blame my fatigue on me being fat, ignoring that I was fatigued before gaining the weight.
    • esperent 11mo ago
      In the same way that CICO (calories in, calories out) is a hard metabolic rule of weight gain, eating lot of complete protein and lifting heavy things is a hard physiological rule of "getting jacked" . It's conceivable that future drug discoveries could safely reduce the amount of lifting required. But the protein requirements will always remain.
      • cjbgkagh 11mo ago
        Not really, CICO is overly simplified to complete pointlessness. It's all hormonal, if you want to gain mass you can take a myostatin inhibitor which is a class of drugs that have already been discovered. You can also eat protein and lift heavy but that's just another way of managing your hormones.
• asafira 11mo ago
  There is large-enough consensus on this drug for its main use cases (treating diabetes and obesity), but more importantly for this conversation: it's actually quite common for drugs to get new indications after their initial one --- at which point, there might be a new, broader consensus on what the drug is good for. Clinical trials are designed to treat a very specific subclass of individuals; pharmaceutical companies very carefully choose that subclass in an attempt to help ensure the clinical trials are successful, which is a combination of the following: - Positive, statistically-significant results. - FDA approval with those results. - Insurance companies willing to pay for the given treatment. - A decent-sized addressable market. Examples of drugs/medical technologies later getting other indications: - Minoxidil was a drug that only later got its approval to be used as a hair loss treatment; there are currently clinical trials for a more "advanced" minoxidil oral pill for this use case. - Re: GLP-1s: Tirzepatide later got an indication that it effectively treats sleep apnea. There are very many other clinical trials ongoing for GLP-1s, but perhaps most recently, Semaglutide (ozempic) failed to show statistical significance as a treatment for Alzheimer's. - The Galleri blood screening/test. The initial indication they are going for is folk who are at highest risk for cancer (I believe that's individuals between the ages of 50 and 70); however, that's not to say it would be bad for individuals younger or older. But, this is a way to help ensure the earliest product has a successful outcome. These are ones I know off the top of my head, but I suspect an LLM can give several more examples.
  • aksss 11mo ago
    [flagged]
    • rytill 11mo ago
      It really doesn’t, at all. Every sentence has a clear, non-equivocative meaning and it doesn’t use any LLM tropes. Your LLM sensor is seriously faulty.
    • kridsdale3 11mo ago
      I don't agree.
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• bparsons 11mo ago
  There is a growing body of evidence that this is the most significant class of drugs since the introduction of statins. Whatever it is doing, it is delivering tens of millions of quality adjusted life years.
• tracker1 11mo ago
  All I know is I had some miserable side effects that started after a couple years that just progressively got worse while on them... when I found out it was the Trulicity/Ozempic I stopped, and the effects coming off were nearly as miserable... took almost a year to recover coming off and still dealing with the fallout.
  • mikaraento 11mo ago
    I’m sorry you went through that
  • basisword 11mo ago
    Curious how you tied the side effects to GLP-1 when they didn't appear for a year and took so long to go away after stopping? Is it possible it was unrelated?
    • tracker1 11mo ago
      It took about a year and three specialists... Mostly just tried to treat the symptoms. I found it when I found out about the lawsuit against Trilicity and put 1 and 1 together. I've still got some digestive problems almost 2 years since stopping.. but it's not as bad. The 24/7 sense of starvation stopped after about a year and gaining 80# over when I started them. I put Trilicity and Ozempic together as I was on both at one point due to availability issues... Which disqualifies me from active participation from both class action suits. I've had some of the worst interpretations of a lot of medications before but nothing like this... For the rest of my life, I'm unlikely to take any new prescriptions from here forward... I'm mostly managing my diabetes with a meat based diet and minimal supplemental insulin. Many days I don't need any. But gluconeogenesis will build up after a few days, even if I haven't eaten. The more I've looked into it, the more I feel T2D is here treated with Keto/Carnivore over pharma intervention. Doesn't make it easy and environmental issues happen... I cheat about one meal a week and often pay for it.
• doctoboggan 11mo ago
  I had just assumed that all these new things this is a cure for are just down stream affects of being overweight, and losing the weight also reduces the incidence of these other issues as well.
  • johnfn 11mo ago
    One reported benefit from Ozempic is that it improves self control. For instance, there are some studies that show it's easier to stop smoking on Ozempic[1]. I can't think of any way that would be modulated just by being less overweight. [1]: https://www.goodrx.com/classes/glp-1-agonists/semaglutide-for-smoking-cessation?srsltid=AfmBOop93LKZ1geu_EmATI83VPbOvuhIwOJIS6NO_7l0hAUbD5S3QYGJ https://www.goodrx.com/classes/glp-1-agonists/semaglutide-fo...
    • testing22321 11mo ago
      Once you have proven to yourself you can eat less and lose weight, you believe you can do the same with other things like smoking. Makes sense
      • barrenko 11mo ago
        That's not how it works.
        • phil21 11mo ago
          There is not enough evidence to say this is true. It could absolutely be a factor in the effectiveness. Placebo is a highly effective drug. I say this as an extreme evangelist of GLP-1s. Behavior modification and habit building appears to me to be a large part of it. Friends on it who have used to as a performance enhancing drug to change habits have generally stuck with newly developed habits even coming off the drug. Friends who used it as a magic weight loss drug largely returned to previous weights and poor health, even some maxing out the doses over time.
    • sheepdog 11mo ago
• renewiltord 11mo ago
  It's just that when something is widespread enough you can actually study other effects it has. Sort of like how psilocybin and weed had all these other effects but we couldn't study them till they got a little less criminalized. All sorts of shit does stuff, but we grandfathered in substances and froze everything for a while. Then COVID came along and a bunch of people started doing telemedicine and before you know it compounding pharmacies were handing out GLP-1RAs as a substitute for the phentermine they were passing out. Not scheduled, absolutely effective, great stuff. Then with all that use in the wild you could rock and roll. Only problem is that off-label use like me with my retatrutide makes some population studies less effective than before.
• deleted 11mo ago
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• ascorbic 11mo ago
  There are currently several hypotheses. Some say that it's just because it helps you lose weight, and obesity increases the risk of so many things. However while this is true, there are lots of examples where there are effects even when you control for weight loss. One of the more interesting theories is that it's down to their anti-inflammatory effects, because chronic inflammation is linked to so many conditions.
  • deegles 11mo ago
    but are the GLP-1s reducing inflammation or is it a side effect of the reduced caloric intake? does it matter?
    • oracleclyde 11mo ago
      I concur. I too, am on the shots, and after stabilizing my sugars and blood pressure, my chronic migraines have all but disappeared. My migraines have been with me since I was a child, but uncontrolled diabetes and blood pressure were definitely a trigger for mine.
  • buu700 11mo ago
    Aside from fat loss, my guess is that what we'll ultimately find is that the benefits of GLP-1 therapy are primarily due to reduced blood sugar and/or ketosis, either/both of which (along with fat loss) could contribute to improved mitochondrial health and lower chronic inflammation. That could in turn improve all sorts of symptoms, not least of which would be migraine and depression.
    • phil21 11mo ago
      > my guess is that what we'll ultimately find is that the benefits of GLP-1 therapy are primarily due to reduced blood sugar This is my guess as well. It's been eye opening correlating on/off GLP-1s, wearing a CGM (blood glucose monitor), and seeing how that data changes depending on what I eat and how that further impacts what I eat an hour or three later. Tightly controlled blood sugar was life changing to me - and I wasn't diabetic or at risk to become so.
• jorvi 11mo ago
  The Alzheimer """cure""" claim was already disproven by another study. Aside from that, the people who stop taking GLP, 75% gain 50-75% of their bodyweight back and lose all concomitant cardiovascular, cancer etc. risk benefits. No research out on, say, alcoholism yet, but I'd hazard a guess the results are the same. This is not a cravings loss drug but largely a cravings management drug. Which is still pretty great but it saddles healthcare funding systems with an enormous burden for the next 20 years. Or you keep it private, which means you introduce an enormous gulf of health inequality. I hate that our solution to obesity is not the way Iceland treated it's youth drinking problem: reduce access to the harmful thing, give people money and support to do the healthy thing. Stick with it instead of cancelling the program if it doesn't show results in 4 years. Modern food (started in the 80s) has carefully been engineered to be as addictive as possible, health consequences be damned. Let's start fixing the problem there.
  • leoh 11mo ago
    Effects on Alzheimer’s have not been disproven; it was shown that there wasn’t a perceivable benefit from oral semaglutide at the doses prescribed for folks with a certain degree of progression of the disease.
  • SubiculumCode 11mo ago
    It should be treated like other important drugs. The U.S. buys the patent (or other variant) letting it become generic
  • philipkglass 11mo ago
    This is not a cravings loss drug but largely a cravings management drug. Which is still pretty great but it saddles healthcare funding systems with an enormous burden for the next 20 years. Semaglutide goes off-patent in 2032 in the US, and in 2026 in Canada and China: https://journals.library.columbia.edu/index.php/stlr/blog/view/653 https://journals.library.columbia.edu/index.php/stlr/blog/vi... https://www.ncbi.nlm.nih.gov/books/NBK602920/table/t03/ https://www.ncbi.nlm.nih.gov/books/NBK602920/table/t03/
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• mise_en_place 11mo ago
  It's Gila monster venom. You may become a druid while taking it.
• m463 11mo ago
  Reminds me of aspirin. It started from willow tree bark thousands of years ago. I'm pretty sure it was not understood for most of that time either. I wonder when the first person understood how it worked. (if anyone understands it now?)
• didibus 11mo ago
  It's too soon to really know the downsides. Statins for example only recently are better understood and there's a lot more downsides we know about now. It's likely going to be true for GLP-1 as well.
  • apple4ever 11mo ago
    I don't know if it will. These drugs have been on the market for decades.
  • throwaway2037 11mo ago
    The downsides of statins? This is the first I heard about it. Google AI tells me: > The main downsides of statins include muscle pain, weakness, and fatigue, and a small increased risk of developing type 2 diabetes. Are there others?
  • array_key_first 11mo ago
    The downside of statins are more or less made up by people who want to convince you that you can prevent heart disease by taking their magic supplement (which isn't like other supplements, this one really works!) Either that or out-of-touch fitness people who push overly restrictive diets and workout plans. Which work, but actually no they don't, because nobody with a sane mind would want to stick to them. And now you're back at square one but you also have a disdain for food and exercise.
• hammock 11mo ago
  Anything dealing with the signaling systems of the body (GLP-1 agonists, DP-XX binders like Keytruda, IL-XX binders like Humira, etc and even HRT) all fall under this bucket. We have a great understanding of some effects of some signaling systems and we use that understanding to our advantage. But the fact is these signaling molecules and receptors do a lot, more than we know, and in overlapping and complex ways, that we are always finding “new indications” and “new side effects” with roughly equal frequency.