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- Hacker News
- Semaglutide reduces appetite.
The less appetite you have the less you eat crap. The less crap you eat the healthier you are.
There's a little more to it than that obviously but this is the reason that they're finding all these "unexpected" things improving when people take semaglutide. Most food eaten by most people with access to semaglutide is crap, that makes you unhealthy. Eating less crap improves lots of factors.
But the good news is, eating less crap makes you less unhealthy independent of other factors too.
by JimRoepcke - Better summary:
Two years of semaglutide treatment appears to substantially slow the worsening of a blood protein signature associated with future dementia risk
by pagutierrezn - I swear, Semaglutide is reverse Asbestos.
It's something we found and started using to one specific problem, but it later turned out that it has lots of other, extremely wide-ranging consequences. Except that in this case, these consequences are positive.
by miki123211 - Calling it now, the downside is the effects are most apparent on higher dosages, but you cant take higher dosages forever. Eventually you run out of body fat, have go reduce the dose, and the benefits dither.by swalsh
- Semaglutide reduces appetite. Who could have known that eating less will have positive effects?
Maybe we should try consuming less in general and see what the effects are. Is there a semaglutide for my shopping habits? Maybe ban ads?
by amelius - That's a big percent for something that is completely devastating. This is objectively good news.by 1970-01-01
- Isn't lower calorie consumption in general correlated to longevity? (Assuming no major malnutrition)by goda90
- Sure, but there is nothing in the world of the last 30-40 years that can compare to GLP-1s in terms of helping people consume fewer calories. This is a very coarse statement, but I'm confident in making it: there is nothing healthier than being skinny, and GLP-1s make people skinny in a way that is unique in modernity. Our modern food systems are optimized to encourage people to consume as many calories as they can, and GLP-1s are bulwarks against this system, if you will.
- This is interesting. Diabetes is a well-known risk factor for dementia.
- Western disease and sugar heavy diets broadly speaking, which Semaglutide is a countermeasure against. Not yet a vaccine, but in due time (probably via gene therapy). Fructose also helps cancer metastases and spread.
https://www.sciencealert.com/common-sugar-appears-to-loosen-...
by toomuchtodo - As is being sedentary - there are probably lots of interconnected factors in play, and GLP-1 receptor agonists seem to help with more than one (perhaps even many) of them.
Unpicking the exact chains of causation is likely going to be extremely complex, but the general picture continues to look good.
by roryirvine - I'm a strong proponent of GLP1. But a change in one marker is at best an okay signal. But the only thing one cares about is real changes in rates. Who cares about markers that don't translate to real clinical outcomes. That's the whole damn problem with everything from stupid "this makes you younger" claims and the tragedy that is the history of Alzheimer research.
I wish they compared straight-up weight loss without disease. In this specific population, the bias has a known direction: unintentional weight loss in older adults is a well-documented dementia prodrome = weight starts dropping years before diagnosis. So placebo-arm weight losers are enriched for people already on the downward trajectory, and any comparison matched or adjusted on BMI change-diff inherits that, making the drug look better than it should in this study design.
And the 5-year OR 0.74, and no BMI-adjusted coefficient is given for it. The 5-year calibration is dominated by near-term inflammatory/metabolic pathways — exactly what weight loss moves, so it plausibly attenuates much more than 28%.
I think the conclusion is not warranted at all: that semaglutide does more than its weight loss explains, not the same or less. Which is also the commercially valuable claim. And note that Novo funded the study, AND two authors are Novo employees/shareholders.
In short, I like GLP1s, but I'm not convinced by this study that GLP1 treatment reduces dementia incident rates meaningfully compared to normal health weight loss.
by jtrn - Diabates can harm the brain either indirectly, through vascular damage, or directly through nerve cell degeneration. The latter is a less studied mechanism and can explain the benefit from GLPs. But I agree, it's not different than a low calorie diet. In the modern times of abundance and sedentary lifestyle, fasting makes wonders. So, if you have even one vascular risk factor, just cut your calories in half, just stop eating. Your body will thank you.by tsoukase
- GLP-1 provides the only plausible way to do so.by anovikov
- tdlr: This is a Novo Nordisk-funded study focusing on predictive biomarkers rather than real-world dementia cases. Novo Nordisk's actual dedicated clinical trials for Alzheimer's completely failed to show that semaglutide stops cognitive decline.
"A predictive biomarker is like a "check engine" light on your dashboard. It warns you that there is a risk of a future problem. In this study, the researchers only checked if the drug turned off the "check engine" light (by measuring blood proteins), rather than testing if the car was actually driving properly (by testing the patients' actual memory and brain function)."
Always do FIRST analysis on studies. Or have AI do it for you. I used Gemini to dig into this:
"Novo Nordisk funded this study, and several of the researchers are employees or minor shareholders. While corporate funding doesn't automatically mean the data is fabricated, it does mean the company is highly motivated to find and publish data that makes their blockbuster drug (semaglutide, marketed as Wegovy, Ozempic, and Rybelsus) look like a preventative treatment for a wider range of conditions, expanding its market and driving up profits."
"Funding: The study was funded by Novo Nordisk A/S.
Investigation: Researchers conducted a post hoc analysis using data from the randomized, placebo-controlled SELECT trial. They applied the Dementia SomaSignal Test (dSST)—a 25-protein risk score—to non-fasted serum samples collected at baseline and at week 104 to estimate 5-year and 20-year all-cause dementia risk in patients receiving semaglutide (2.4 mg) versus a placebo.
Results: Semaglutide significantly attenuated the progression of the dementia risk signature. Compared to the placebo group, the 5-year predicted risk increased 2.5-fold less (a 26.0% lower predicted event rate) and the 20-year risk increased 1.67-fold less (an 8.8% lower rate). Semaglutide also lowered the odds of patients moving into a higher dementia risk category by 36%.
Subjects: The analysis included 2,970 older adults aged 65 and older (mean age of ~69.7 years) who had overweight or obesity and cardiovascular disease, but no history of diabetes. The cohort consisted of 814 women (27.4%) and 2,156 men (72.6%).
Time: The study evaluated data over a 104-week (2-year) follow-up period. The analysis was published on August 8, 2026."
And then map the weakness to each respective letter if you want to dig deeper.
by bariswheel - So translated to human, does this basically mean then that semaglutide distorts dementia-predictions by altering the related biomarkers, rather than actually help with dementia?by perching_aix
- Didn't even bother looking into it because there's obviously not enough data yet to say anything substantial about GLP-1s and Alzheimers. But your comment should probably be the top.by TheBlight
- Factoring out the ad corpus yelping, the interesting counterpoint is that suppressing the risk signal isn't a good thing if it doesn't suppress the risk.by inopinatus
- Regarding “actual tests”: My team and I built a battery of longitudinal cognitive assessments useful for testing memory and brain function. (http://getNeuroUX.com)by dr_dshiv
- This is one of the most distinguished peer reviewed journals on Alzheimer’s and dementia. Adults know not to make too much of a study of this scale and ambiguity. But considered as such, the paper is above suspicion.by applicative
- The fact that NN funded this study is very relevant but is not necessarily a negative as you make it out it to be. Perhaps that is not your intention but reading the comment made it look like that way.
1. It makes sense for companies that profit from their drugs to use their profits to also commission such studies.
2. Faking data or causing harm exposes these companies to total black swan events for which they will pay dearly so they often have incentives to release anything that might harm their patients.
- Not only that but high intakes of added sugars and fast-acting, high-glycemic carbohydrates are linked to an increased risk of cognitive decline and dementia. Excess simple sugars, particularly fructose and sucrose, promote insulin resistance, chronic inflammation, and vascular damage that impair brain function and accelerate neurodegeneration. So with other words, you diet is a major contributing factor here. The medical establishment and big pharma simple ignores the fact that the biggest health risk for a human being is the "modern" high sugar diet that Kellogs introduced in the US and spread to the western world (even to Asia at some extent).by dev_l1x_be
- > This is a Novo Nordisk-funded study focusing on predictive biomarkers rather than real-world dementia cases
You act like all this is hidden, but the title of the article and the list of authors makes this self-evident.
> Novo Nordisk's actual dedicated clinical trials for Alzheimer's completely failed to show that semaglutide stops cognitive decline
Sure, but the EVOKE studies were focused on something that could be sold as a product covered by insurance: semaglutide to those who had already developed Alzheimer’s. It is widely agreed the trial failed because it was a population already diagnosed with dementia. There’s lots of studies not funded by Novo that show semiglutatide has reduced the incidence of dementia in the diabetes population. Novo knows that running a general study on whether semaglutide reduces dementia in a non-diagnosed population is useless to their bottom line because insurance will never pay for everyone to take the drug.
by cowsandmilk - If you're overweight or especially if you're T2D I highly encourage you to discuss GLP-1 with your doctor. If you're T2D then get research retatrutide which looks to be an actual cure for T2D by clearing liver fat. It should be released early next year but research-use is available and what everybody is taking. Companies like finnrick do public testing of research peptides and a good place to gather names.
- Semaglutide cleared my liver fat and fixed my moderate NAFLD in a matter of months. Why is retatrutide necessary?by 01100011
- I’m on tirzepatide right now from Eli lily, and I’ve been very interested in Reta, but I can’t say that I jump at the chance to inject something into myself that hasn’t been tested directly on the actual thing I’m about to put into my body. I know there are testing companies that will test certain sources but it’s not like they’ve tested the vial you get. If there’s some kind of pathogen or bacteria or whatever in the vial you get, well, there’s no recourse: it was “for research use only”. That seems like an unacceptable risk, but I see so many people on the internet claiming miraculous results. Maybe if I knew someone in real life, but I know those biohacking subreddits and such are astroturfed to no end by companies looking to sell sketchy peptides.by antinomicus
- I hope Retatrutide pans out but encouraging people to hop on research chemicals when we already have drugs that can get lots of T2D people into remission is a stretch too far. Let's wait for the actual medicines to be produced by legitimate manufacturers instead of ordering grey market peptides from some nameless whoever with zero liability. This is absolutely not on the right side of the risk-reward equation. Mounjaro is more than good enough.
- I'm a big semaglutide proponent after being on it for a year. I know research says it helps with inflammation, arthritis (separately from weight reduction), and all sorts of magical things.
I lost 40 pounds in a year(230 to 190) at age 50. Great! I also went from being active and fat(weightlifting with some cardio) to basically having no energy. In the last year I've had arthritis appear in several joints. I'm awake several times a night to pee(yeah, prostate is acting up but I still void completely. The semaglutide is like a diuretic for me at night.). I get waves of hypoglycemia like feelings where I feel weak and spaced out. I'm afraid to get off of it because now my joints can't handle the extra weight. My doc recommended going to every other week now that my BMI is normal but as far as I can tell that advice isn't backed up by any research. Anyway, it's a powerful drug that works well but is not without side effects.
by 01100011 - You are a proponent, but your outcomes seem worse?by hattmall
- I'm on the pill version, which allows me to adjust the dosage on a more day-to-day level. It also doesn't need a fridge, so it allows me to travel more easily. There's a level that works best for me long-term, and it's quite a bit less than typical.by zulux