9 ms·

So has anyone managed to separate the effects of semaglutide from the effects of weight loss? If this is caused by the weight loss, it is a little disappointin

• a-dub 1mo ago
  that is the interesting question. also the effects of weight loss vs. the effects of disengagement with the engineered to be addictive "food products" side of the western diet.
  • lotsofpulp 1mo ago
    What is interesting about it? Proper sleep, eating less (including liquid calories), and exercising have been the mainstream medical advice for many decades. Obviously, most people can’t accomplish that for whatever reason, so another solution was needed.
    • a-dub 1mo ago
      > What is interesting about it? did western society engineer a junkfood-industrial-complex so addicting and so en-sickening that it ultimately required a sort of junk food methadone to wean itself off?
      • dbalatero 1mo ago
        I mean kinda yeah
• object-a 1mo ago
  What should public health have done differently?
  • hattmall 1mo ago
    Treat junk food like cigarettes
    • bobthepanda 1mo ago
      Unfortunately in most countries the blocker is politics, not the desire of public health officials to do anything. See the current US admin going after vaccines while declaring open season for peptides.
    • p_j_w 1mo ago
      People have tried. Any time the government tries to do anything a substantial portion of the electorate throws a childish hissy fit and tries to make out that the Bolsheviks are coming to make their fries less tasty for no good reason.
      • apparent 1mo ago
        What's interesting is that it's different parts of the electorate that get upset. When Republicans wanted to make junk food/soda ineligible for food stamps, Dems got upset. And when Dems wanted to tax large sodas, Republicans/libertarians got upset. I think the former makes much more sense than the latter, since it is literally being funded by the govt. That's a reasonable first step, or possibly only step, especially considering that most people on food stamps are also on govt-funded/subsidized healthcare (meaning taxpayers will end up footing the bill when they require expensive treatments resulting in part from an unhealthy diet).
        • llm_nerd 1mo ago
          This is a pretty insincere take.
          • apparent 1mo ago
            Feel free to elaborate on my alleged insincerity. Was I insincere in noticing that there are partisan patterns at play, or insincere when pointing out that the govt should have more control over govt-run/taxpayer funded programs, as opposed to transactions between private parties? I am sincerely curious to know your opinion.
• emmabruns 1mo ago
  Even more so. Not absolute weight loss but the effect of loss of the systemic inflammation due to a surplus of visceral fat which has significantly more systemic effect than subcutaneous fat or other types of loss of mass.
  • criddell 1mo ago
    I'm not overweight but I've been thinking about getting a low does glp-1 for the supposed inflammation improvements which could be neuroprotective. The side-effects seem minor and if it doesn't agree with me, I can just stop since I'm not using it for weight control. I've never really read much about people using it in this way though and I'm somewhat risk averse, so it's easy for me to keep procrastinating on getting the prescription.
• siva7 1mo ago
  >> If this is caused by the weight loss, it is a little disappointing that public health didn't act quicker I imagine people hundred years in the future will think of our current society rightfully as dumbfucks. But should we be surprised? 50 years ago women didn't have voting rights; homosexuals were incarcerated in western societes; all because of moral and power implications of some powerful men. Not much different with Semaglutide.
  • kbelder 1mo ago
    >50 years ago women didn't have voting rights Where are you? In the US, women have had full voting rights for over 100 years.
    • siva7 1mo ago
      No, black woman (among many other minorities) certainly didn't. I guess that part isn't taught in american schools as thoroughly as it should be.
      • clipsy 1mo ago
        If you're seriously claiming black women didn't have the right to vote in 1976, you should probably provide some evidence rather than snide remarks.
        • siva7 1mo ago
          Then teach us.. when did they got actual voting rights? (i'm not trying to be snarky but sometimes it' not easy seeing the level of history ignorance in society)
          • codingdave 1mo ago
            Federally? 1920. When did all the voter suppression become illegal? 1965.
          • clipsy 1mo ago
• SoftTalker 1mo ago
  With all the research into dementia and its causes, if there was a simple strong link to overweight I can't imagine that would not stand out in the data and be well known by now. Edit: although, there are well-known links between overweight and a lot of negative outcomes, and yet people are still too fat.
  • junofan 1mo ago
    [dead]
  • fcarraldo 1mo ago
    Nearly 75% of Americans are overweight. (over 30% 'overweight', over 40% 'obese'). Obviously, 75% of Americans do not develop dementia. Do more who are overweight develop dementia than those who are not? Well...it's hard to say when 3/4ths of the population is overweight.
    • brians 1mo ago
      Actually that makes it really easy to tell. If one side were very rare maybe we’d miss a subtle effect. But at 3:1 we should see plenty!
• Aurornis 1mo ago
  That is the question now. Some studies have some early evidence that GLP-1s might reduce inflammation markers a little more than weight loss alone. Giving GLP-1s to normal weight people doesn’t work well because they can have to work harder to maintain their weight. That can be a real problem as people get older where maintaining muscle mass is important for quality of life and longevity. I remember how hard it was to keep some of my grandparents at a healthy weight, so adding a GLP-1 to a non-obese elderly group is a no-go for study purposes. Going to be hard to separate these effects out.
  • WarmWash 1mo ago
    My assumption was that GLP-1's don't suppress appetite so much as suppress the compulsion to eat when not necessary/more than necessary?
    • tiahura 1mo ago
      It’s both. That’s why it’s so effective.
    • eapressoandcats 1mo ago
      They also clearly have some impacts on metabolism. It’s well known that a challenge with dieting isn’t just eating less, it’s metabolic changes that make weight loss harder. GLP-1’s avoid that.
      • gruturo 1mo ago
        They do slow down the metabolism, yes. They seem to also act on some reward mechanism - making some stuff (not just food. Alcohol, gambling, porn, smoking, other drugs have anecdotally been reported to feel less attractive / addictive) have a reduced pull on one's will. They also measurably delay gastric emptying - to the point that some medicines, meant to be taken on an empty stomach, are not safe to take within up to 3 hours from the last meal, compared to one hour or so for other people.
        • 1mo ago
• kwanbix 1mo ago
  Well, if you consider that is much cheaper to eat trash than healthy, and that food companies' only interest is in maximizing profit, you have what we have.
  • WalterBright 1mo ago
    I don't buy that. You can buy a steak and a potato for two for less than a bag of Doritos. A banana costs far less than a candy bar. A bag of mixed nuts will provide many meals. Price out a bag of rice, a bag of beans, etc. > food companies' only interest is in maximizing profit Pleasing your customers is how profit is maximized. Besides, I bet if you were faced with two stores, one that charges $x for A, and another that charges $(x-1) for A, you'd patronize the latter store.
    • dbalatero 1mo ago
      Where are you getting a steak and potato for 2 for less than a bag of Doritos? Is it a 50 lb bag of Doritos?
      • jambalaya8 1mo ago
        Maybe it's 4oz of very lean tough steak and a single small russet potato with no fat, and the two mentioned are five year olds.
      • to11mtm 1mo ago
        .... At least 10 to 15-ish years ago, I would actually be closer to agreeing; You could get Cube or Chuck steak for 3-5$ a pound and potatoes were cheap as hell too. Toss some diced onion in and You'll have a good dinner. How do I know? Well I grew up in a family where for... reasons[0] we were not that well off for quite a while. Cube Steak was one of the big things we did for a family meal that Dad cooked. (Chili was his other favorite to make, which was also cheap to do for how much food came out of it...) However the current prices of beef, I feel like you'd need to have a long standing personal relationship with a local butcher or rancher to make this true. [0] - My mother's over-propensity for being truly Christ-like in her charity to family and others, also sending myself and my three siblings to Catholic school to avoid the then-absolutely-failed Detroit Public school system were major factors.
• RobotToaster 1mo ago
  Alzheimers dementia is sometimes called type 3 diabetes, so it may be both.
• SecretDreams 1mo ago
  Dementia aside, there are plenty of very obvious reasons we should have been discouraging obesity and encouraging healthier eating and lifestyle habits. Lobbies and general government ineptitude have been a problem longer than obesity and that one needs to be solved first.
• jaggederest 1mo ago
  I have some individual anecdotal evidence. I spent a long time, basically a year, relatively heavy but on a very small dose of GLP drugs due to tolerability issues, and my labs improved dramatically, to a degree we redid them out of disbelief, even without weight loss. I believe one of the suspected underlying causes is reduction in fatty liver despite constant body weight and composition, and also inflammation reduction directly through GLP influence in other areas of the body. I'm not great evidence because N=1 and all the confounders, but I found that it absolutely made me much healthier without weight loss. I then went on to increase the dose slowly and have lost a bunch of weight and my labs improved even more, which I attribute mostly to the body mass reduction.
  • alyandon 1mo ago
    Similar experience here on minimal dose of GLP-1. There is definitely something going on here other than "you are just losing weight and that's really why you are healthier". With my labs at my current weight you can not tell that I am a type 2 diabetic. Previously, when I was at this very same weight in the past - all my labs indicated I was prediabetic.
    • aucisson_masque 1mo ago
      Could be just because you stopped eating bad food. Things improve dramatically once you limit your intake of industrialized food.
      • preg_match 1mo ago
        Not that dramatically. Things like fatty liver take a long time to reverse. It’s not like you stop eating junk food and then suddenly your body is chilling. No, the damage is done and takes a long time to repair. It’s like smoking. You can benefits from quitting smoking within 20 minutes. But to reach the full benefit and reversal, you need 15 years.
        • basilgohar 1mo ago
• ivraatiems 1mo ago
  Semaglutide was invented in the early 2000s. Weight loss is an extremely complicated and societally mediated problem that we didn't have a 'cheat code' like this for until recently.
  • cyberax 1mo ago
    Semaglutide was patented only in 2018. The previous medication was liraglutide. It behaved similarly but had a half-life of only a few hours. It required daily injections, and you could feel its effects wax and wane throughout the day.
  • hypertele-Xii 1mo ago
    Weight loss is extremely simple. The human body has two mutually-exclusive metabolic modes: burning sugar, and burning fat. Mode switching is automatic: if you eat sugar, your body runs sugar-burning mode and any fat you eat at the same time is stored. To lose weight, simply don't eat sugar; your body auto-switches to ketosis and burns fat reserves. Foods with both sugar and fat make you gain weight, e.g. ice cream is 50% sugar 50% fat. Eat ice cream every day and you'll only gain weight. The only "social problem" we now have is that women are on a power-trip rebelling against the men who used to keep them honest about eating. Hence "body positivity" from feminists.
• atomicnumber3 1mo ago
  But... the profits!
• wincy 1mo ago
  My wife has hardly lost any weight from Zepbound but she went from having such intense back spasms she could maybe walk a few hundred feet at a time to being able to easily handle a week at the Disney World parks on foot. Before she had to rent a motorized scooter. Absolutely life changing for her.
  • criddell 1mo ago
    That's awesome!
• throwaway82931 1mo ago
  All my immediate family members are obese. I'm not (BMI 24.5, borderline overweight at the high end of normal, highest lifetime BMI was 29.5), but that's through strenuous, exhausting effort over decades. I also exercise regularly, though I've learned over time how disconnected exercise is from weight management. At my weight, I'm not a candidate for going on a GLP-1. I'm sure I could find an unethical doctor to prescribe it if I looked hard enough, but I don't want to have the downsides hidden from me. My weight has been steadily ratcheting up over the years, since I don't have as much room in my life as I used to for living with the discomfort of caloric deficit. If that continues, I will probably become a candidate for GLP-1s, like my immediate family members, just after a decade or so of possibly unneeded striving. Lots of people are in situations far worse than mine, so I don't feel unlucky — but it would be nice if there were a clearer path forward. While lowering risk for Alzheimer's is not a priority for me, other effects of GLP-1s sound extremely enticing — especially reports of reduced food craving.
  • swalsh 1mo ago
    You can probably get a prescription for a low dose, but you'll be self pay.
  • jaggederest 1mo ago
    Speaking as someone who had the same kind of reservations, I think you sound exactly like me, and if I had any advice to my past self, it would be "get on it as early as it's available, start much lower than anyone thinks is sane, and never ever stop". I got a concierge doctor who absolutely evaluates what I ask for skeptically, and pay for my GLP medications out of pocket, so I feel ethically totally comfortable with this position. The downsides are real and significant, it's not a "fun" medication, but just the change in how I feel is worth every penny, let alone the massive reduction in heart attack risk, liver enzyme numbers, and so on.
    • Jaygles 1mo ago
      What downsides have you experienced?
• loeg 1mo ago
  > If this is caused by the weight loss, it is a little disappointing that public health didn't act quicker Public health has been trying to get obese people to lose weight forever, what are you talking about. We've known it's bad in enough other ways. It was just really, really hard (at a population level).
• Muskwalker 1mo ago
  > So has anyone managed to separate the effects of semaglutide from the effects of weight loss? I was looking for that in particular. The study does say: "To assess whether the observed effect was mediated by weight reduction, we performed a sensitivity analysis adjusting for change in BMI from baseline to week 104. In this adjusted model, the treatment effect coefficient was attenuated from β −0.092 to β −0.066 (P < 0.001), corresponding to a reduction of 28% in the estimated effect size. This attenuation indicates that 72% of the treatment-associated difference in 20-year dementia risk persisted after accounting for BMI change, suggesting that mechanisms beyond weight loss contribute to the observed proteomic signature modification."
• paulpauper 1mo ago
  it is a little disappointing that public health didn't act quicker - lots of people have been overweight for a century now, so literally 10's of millions of people could have been saved from dementia had action been taken 100 years ago Given that the drug did not exist until only recently and it took decades to develop with the latest of technology, I don't see how this could have been possible. Stomach surgery has been around for 50 years though, but it's a bigger undertaking than an injectable drug.
• cthalupa 1mo ago
  > So has anyone managed to separate the effects of semaglutide from the effects of weight loss? In general? Yes. For this specific thing? We haven't even really shown the effects matter for humans. > If this is caused by the weight loss, it is a little disappointing that public health didn't act quicker - lots of people have been overweight for a century now, so literally 10's of millions of people could have been saved from dementia had action been taken 100 years ago. Public health has been banging the drum on obesity for decades now. But humans on the whole aren't built to be able to resist hyper palatable calorie dense cheap foods.
  • OptionOfT 1mo ago
    We're too soft on companies, but equally too hard on people who have a food addiction.
    • SubmarineClub 1mo ago
      [flagged]
      • ThrowawayTestr 1mo ago
        It's really not hard to not drink. It's really not hard to not do heroin. It's really not hard to...
        • procaryote 1mo ago
          Those are easier in many ways as you don't need heroin or alcohol to survive and can avoid it completely If it's hard or not is more of a philosopical question about how much free will we have as people. Statistically they're all hard and not over-eating is the hardest. Culturally and individually we do a lot of things that probably make the food one even harder If you drink too much, the common answer is that you need to stop drinking. If you eat too much, we are very reluctant to talk about how you need to eat less. We prefer to talk about how it's someone else's fault and how powerless we are to do anything about it, including comforting lies about how eating less wouldn't work anyway, or how being overweight isn't bad really.
• christina97 1mo ago
  GLP-1s seem like a night and day difference in intervention adherence though. For various obvious and non-obvious reasons, it’s very hard to produce an intervention that people will adhere to to make the test group lose weight.
• cloudie78 1mo ago
  It’s in broad terms weight loss related. More specifically blood glucose and insulin regulation which can be out of whack even if you’re not diabetic on paper. This is why you’ll see people claiming they’re not diabetic but still saw improvement from Ozempic and friends. Their insulin and glucose regulation was spoke. in casual terms “fucked”. GLP-1 receptor agonists such as semaglutide act partly through the brain to reduce hunger, increase satiety, and lower spontaneous energy intake. Sustained caloric reduction produces weight loss, including loss of visceral fat around the abdominal organs and ectopic fat stored in tissues such as the liver. These fat depots are metabolically active and contribute to insulin resistance through excess fatty-acid delivery, inflammatory signalling, and disruption of normal insulin action. As they shrink, muscle and liver tissues become more responsive to insulin, so the pancreas no longer needs to secrete as much insulin to maintain normal glucose levels. This reduces the compensatory hyperinsulinaemic state that can exist for years before diabetes develops and decreases the probability that impaired glucose regulation will progress toward overt type 2 diabetes. Those changes propagate into the cardiovascular system. Better insulin sensitivity and lower visceral and liver fat are commonly accompanied by lower triglycerides, improved blood pressure, reduced systemic inflammation, and better endothelial and vascular function, thereby reducing several mechanisms that contribute to atherosclerosis and cerebrovascular injury. GLP-1 receptor agonists also have a direct metabolic action independent of weight loss: when glucose is elevated, they enhance pancreatic insulin secretion and suppress inappropriate glucagon secretion, improving glucose control without forcing insulin secretion when glucose is low. The overall effect is therefore a combination of an immediate GLP-1-mediated improvement in appetite and glucose regulation followed by progressively larger downstream effects from weight and fat loss, which together reduce the metabolic and vascular abnormalities associated with cardiovascular disease and, over much longer periods, potentially with dementia risk.
  • jvidalv 1mo ago
    [flagged]
    • acuteaura 1mo ago
      There is a fine line between being opposed to fat acceptance and thinking performative cruelty works. (It's does not. It made me so much worse. I have nothing but bad things to say about the medical "professional" who catastrophized my diagnosis to "wake me up" and then shrugged when my response was depressed resignation.)
• jjallen 1mo ago
  It’s been no secret that being fat is terrible for us. It’s getting people to actually eat less is the hard part.
• inglor_cz 1mo ago
  There are some effects of GLP-1s which definitely cannot be explained by weight loss. For example, some patients report that they lost their compulsive habits - gambling, shopping etc. In some, the effect is so extreme that it flips into outright anhedonia, an inability to enjoy anything. GLP-1s are ultimately treatments that act on our neurohumoral regulation, and hormones tend to have a lot of functions all around the body. Claude would say that the expected "blast radius" of fiddling with hormones is much bigger than that of just losing weight.