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.
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.
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 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.
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.
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 your 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.
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.
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.
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.
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.
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.
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?
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.
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.
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.
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.
>> 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.
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.
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.
Retatrutide has a specific mechanism for clearing liver fat (glucagon) which makes it one of the most effective ways to treat T2D. This is the 3rd agonist not found in semaglutide or tirzepatide.
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.
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.
Is it kind of the stuff where the benefits outweigh the side effects? I'm just scared of the unknowns with the drug with such overwhelming positive research. Maybe, I'm a paranoid person but I'm unable to believe that such a powerful drug isn't without any side effect, clinically proven.
Although it's encouraging, they do mention that the reduction in the BMI also have an effect (they take it into the consideration by lowering the β −0.092 to β −0.066 (P < 0.001)).
Just skimming through it, it's possible there are direct benefits, but it could also be other environmental factor. This study will most likely generate others that give us more insight in the future.
Read a interesting piece recently that Semaglutide reduces inflammation, and very likely the weight-loss and a lot of the other emerging benefits are likely the effects of reduced inflammation.
> and very likely the weight-loss and a lot of the other emerging benefits are likely the effects of reduced inflammation.
That’s not correct. GLP-1s interact with satiety (fullness) circuits and reduce appetite. They also have minor effects delaying gastric emptying, meaning the stomach stays full longer.
There is some early data suggesting that they might reduce some inflammation markers slightly more than weigh loss alone, but losing weight and controlling food intake without GLP-1s reduces the same inflammatory markers. The question now is if GLP-1s have additional anti-inflammatory influence.
I don’t know why someone would claim all of their effects are downstream of inflammation. Some people get stuck in modes where they think inflammation is the cause of everything and can’t comprehend causal effects going in the other direction.
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.
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.
First of all it’s a nice study. The dosages they always give are way too high and mice are rarely a reliable model.
But you’re also ignoring the fact that the same study shows that glucose inhibits the behavior.
So your claim that the study indicates its sugar is incorrect. The study indicates a possible impact from fructose which is countered by glucose, so the real issue is the fructose to glucose ratio.
Table sugar providing equal fructose and glucose molecules is acquitted by this study.
Also age plays a pretty significant role. I know older asians who regularly walk who still got T2D. You could argue that walking isn't physically active enough... but they'd argue otherwise. It's all relative.
At the risk of being argumentative I had a horrible diet for the past ~10 years and carried 50 extra pounds. However I also exercised a lot as a hobby and to my shock my glucose and other bloods always came out in the normal range.
This year I started Mounjaro and dropped the 50 pounds. Curious to see what my next checkup shows.
People kick around the idea of the "personal fat threshold". E.g. caucasians seem to be better at carrying fat than, say, Southeast Asians. White people seem to be able to better store fat without metabolic side effects; SEA seems to get T2D at a much lower bodyfat percentage.
Just pattern matching as an autistic human. Similar results were seen on a ketogenic diet (and to some extent, intermittent fasting). What do they have in common? Sugar intake reduction. Is it surprising sugar potentially fuels cancer, contributes to dementia, etc? It shouldn’t be. It’s indirect and a casual connection.
There is no health benefit to a high sugar or Western diet, only downside. I think calling it poison is hyperbole, but it’s definitely not healthy, based on all available evidence. I expect to see longitudinal scale results over the next decade as everyone starts taking GLP-1s.
(I take a glp-1, they’re an amazing drug class, it changes how your brain operates, charlie day waving arms in front of a whiteboard meme here)
Thats due to caloric restriction. A high fat diet isn't going to helpful as well. To think that people cut sugar but continue to eat far too much meat and fat... yikes.
"Semaglutide attenuates a proteomics-based dementia risk signature "
ie : clinically meaningless.
The company behind this, Novo Nordisk is increasingly desperate, as tirzepatide destroys the semaglutide revenue stream and the consequent job losses decimate the company
Their operating profit was up 11% on a margin of 44% according to their recent quarterly release, and they beat EPS by 23%. They were in a little trouble in the stock market a few years ago as competitors came online, but they are doing pretty well right now.
They have launched new semaglutide oral products which are growing faster than previous products, and they have multiple drugs in the research pipeline in late phases.
For sure we still need to find out many related outcomes.
Last year it become known that it increases (high relative risk, low absolute risk) non-arteritic anterior ischemic optic neuropathy (NAION), ie sudden, sometimes permanent vision loss.
To save others the click: It increased the likelihood to 1 in 10,000 in adults with type 2 diabetes.
Diabetics are already more prone NAION. This studies contribution was to show that diabetics on GLP-1's are MORE prone. It does not show that the general population is more prone when taking GLP-1's.
I didn't check to see if other studies prove that.
It is well known that forcing a sudden drop in chronically high average blood glucose (like, from 200+ to a normal ish range) with insulin can cause vision loss. I wonder if it's the same mechanism?
"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.
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.
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.
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.
Edit: although, there are well-known links between overweight and a lot of negative outcomes, and yet people are still too fat.
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.
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.
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?
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.
Lobbies and general government ineptitude have been a problem longer than obesity and that one needs to be solved first.
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.
Where are you? In the US, women have had full voting rights for over 100 years.
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.
Just skimming through it, it's possible there are direct benefits, but it could also be other environmental factor. This study will most likely generate others that give us more insight in the future.
That’s not correct. GLP-1s interact with satiety (fullness) circuits and reduce appetite. They also have minor effects delaying gastric emptying, meaning the stomach stays full longer.
There is some early data suggesting that they might reduce some inflammation markers slightly more than weigh loss alone, but losing weight and controlling food intake without GLP-1s reduces the same inflammatory markers. The question now is if GLP-1s have additional anti-inflammatory influence.
I don’t know why someone would claim all of their effects are downstream of inflammation. Some people get stuck in modes where they think inflammation is the cause of everything and can’t comprehend causal effects going in the other direction.
Unpicking the exact chains of causation is likely going to be extremely complex, but the general picture continues to look good.
https://www.sciencealert.com/common-sugar-appears-to-loosen-...
But you’re also ignoring the fact that the same study shows that glucose inhibits the behavior.
So your claim that the study indicates its sugar is incorrect. The study indicates a possible impact from fructose which is countered by glucose, so the real issue is the fructose to glucose ratio.
Table sugar providing equal fructose and glucose molecules is acquitted by this study.
No, just being sedentary. There's no such thing as acquired diabetes in physically active people.
https://www.tri247.com/triathlon-news/elite/lionel-sanders-t...
Also age plays a pretty significant role. I know older asians who regularly walk who still got T2D. You could argue that walking isn't physically active enough... but they'd argue otherwise. It's all relative.
This year I started Mounjaro and dropped the 50 pounds. Curious to see what my next checkup shows.
Note I am not Western
There is no health benefit to a high sugar or Western diet, only downside. I think calling it poison is hyperbole, but it’s definitely not healthy, based on all available evidence. I expect to see longitudinal scale results over the next decade as everyone starts taking GLP-1s.
(I take a glp-1, they’re an amazing drug class, it changes how your brain operates, charlie day waving arms in front of a whiteboard meme here)
ie : clinically meaningless.
The company behind this, Novo Nordisk is increasingly desperate, as tirzepatide destroys the semaglutide revenue stream and the consequent job losses decimate the company
They have launched new semaglutide oral products which are growing faster than previous products, and they have multiple drugs in the research pipeline in late phases.
Last year it become known that it increases (high relative risk, low absolute risk) non-arteritic anterior ischemic optic neuropathy (NAION), ie sudden, sometimes permanent vision loss.
https://www.ema.europa.eu/en/news/prac-concludes-eye-conditi...
Diabetics are already more prone NAION. This studies contribution was to show that diabetics on GLP-1's are MORE prone. It does not show that the general population is more prone when taking GLP-1's.
I didn't check to see if other studies prove that.
1) You must have a crowded optical disc as a precursor (low cup to disc ratio). Genetic and can be tested
2) You have stiff veins/arteries due to poor metabolic/cardio health
3) when blood pressure drops too much, blood flow can get cut off to the optical nerve temporarily due to reliance on high blood pressure due to 2
4) Due to loss of blood flow, optic nerve swells and closes blood flow into the eye due to 1
Which you can get checked for via a $50 optical scan.
No crowded disc, very little risk.
(Cup to Disc ratio of 0.2ish or less starts to present risk)