Comment by bariswheel
1 day ago
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.
> 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.
You seem to be arguing that people shouldn't be skeptical, by default, of studies of products that are funded by the companies that make the products.
They funded this study as a prospective way of increasing the adoption and market share of their trademarked medication. It deserves skepticism.
It wasn't even funded in the way funding a study usually means. That an entity handed over money to a research group. The study was done by employers in their work time for their salary. Its a Novo Nordisk study, and as you say its right there in the open. Pointing an llm against the paper to (wrongly) realize this is a real tragedy of literacy.
I think it rubs plenty of laymen the wrong way to not make it a bit more explicitly known.
The world could use a bit less nuance in our headlines these days.
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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).
I'm not sure how the medical establishment ignores this, from my understanding (and please correct me if I'm wrong as I'm not fact checking myself in this moment) - the association between the two is largely linked to vascular dementia (obesity, hypertension, yadda yadda).
I think it's hard to argue "The medical establishment" ignores diet as an important factor.
I think the reality a lot of the time is doctors prescribe something to help. They can't force a diet change on a patient, and they're not mutually exclusive interventions.
It's easy to say "just diet ez" and it's hard to "just diet".
If you can administer a treatment as a simple one and done thing, that's alright. If it's a pill you got to take every day, that's pretty bad. More than once a day? Horrible. Why? Because a lot of patients just don't have it in them to take a pill 3 times a day consistently.
If it's purely an "exercise willpower" thing or a "change your lifestyle" thing? You might as well give up.
The medical establishment wants to do things that work. Telling people "go diet" doesn't work. Semaglutide, evidently, does.
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You say force a diet change on a patient. OP certainly meant forcing a diet change in the input of American factories. Sugar can be found in fruits. That's the right place. If you need some, use fruits, maybe alcohol. Everything else can be slashed. No sugar in prepared meals anymore. No sugar in pasta anymore. And most of all, no sugar in water. Sugar input makes more damage than cocaine today.
We can call it the Prohibition II. There will be underground bars with sick people binging on sugar. We can change the shape of sugar to prevent restaurants from adding it to food. We can make it bitter. Absolutely need sugar? Eat that lemon-tasting block. We can call it The War On Sugar.
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The medical establishment that I have familiarity with (in the US) pretty much only ever treats symptoms, not causes.
Don't believe me? Next time you go to see your primary care physician, ask them what you should be doing to lower your risk of whatever malady tends to run in your family. (Diabetes, cancer, dementia, etc.) They're going to stare at you in blank confusion for a few seconds before making some vague suggestion about a better diet and more exercise. Guaranteed.
The reasons are many, and detailed enough to write MANY books about, but the low hanging fruit is: we don't have a culture of monitoring and improving our own individual health, physicians are trained almost exclusively to solve problems not prevent them, modern nutrition science is a joke, omnipresent health insurance distorts incentives for everyone, doctors are too overworked to get to know their patients, private equity has captured a large chunk of health care, drugs are positioned as the first line of treatment for almost everything, etc.
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> 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
The medical establishment isn’t ignoring this at all. They’ve been pushing for healthier diets forever. Primary doctors have always been pushing for healthy eating.
That doesn’t mean patients welcome the advice or follow it. Everyone knows that eating high sugar diets and being overweight is unhealthy.
There was some short-live resistance to the idea that being overweight was unhealthy, but that wasn’t coming from the medical establishment. That was an anti-science, anti-medicine movement that went mainstream under a misplaced desire to not make anyone feel bad in any way. That movement has lost steam quickly as an easier option has appeared for reducing appetite and inducing weight loss.
I don’t understand how you’re trying to twist this into a claim that big pharma is ignoring the impact of unhealthy eating. GLP-1 drugs work by reducing unhealthy overeating and cravings for unhealthy foods.
There was a fringe that said being overweight was not unhealthy, but the more salient points were the following:
1. BMI was basically just pulled out of a hat, and it turns out that for many health concerns, the overweight class does better than the normal weight class, with the actual “clearly worse” outcomes really coming up as you trend into obesity.
2. Environmental and genetic factors are huge contributors to people being overweight. To some degree moralizing about weight loss is a bit like telling kids with asthma they should live in places with less pollution. Or telling someone with breast cancer to not have the BRCA gene.
3. Doctors would regularly miss health problems because they’d blame them on people being overweight / not exercising enough. Especially for difficult to diagnose issues, it’s easy to just point at the number you have that “looks bad”.
4. We still have no firm reason why people are gaining weight. The popular answer is sugar and processed foods but those very much already existed at scale in the 50s.
The tragedy is that it turned into a morality play where fat people were blamed for it, despite in many ways being as genetic as getting breast cancer.
The reality is people who actually study obesity know that basically GLP-1s are the only health intervention other than bariatric surgery that consistently works. At a population level no intervention has reversed fattening anywhere in the world.
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> Everyone knows that eating high sugar diets and being overweight is unhealthy.
There is a lack of evidence that the public understands what healthy and healthy effectively mean to their day to day lives,
aside from “looking better”.
Diabetes is well known to be a massive risk factor for dementia - so no, people are not ignoring this!?
More broadly, diet is a frustrating modifiable risk factor - there are lots of studies suggesting the (somewhat nebulous) "Mediterranean" diet is protective, and beyond that, omega 3s.
But human diet is uncontrolled, highly varied, and reporting is difficult to obtain and unreliable (people don't want to admit what they ate), so a lot of these data are seen as interesting, promising but unconfirmed.
They controlled for BMI at least, so they knew that was going to be a common question. BMI is a pretty good proxy for that, and they still said that the majority of the effect came from the compound and not BMI.
Guess what category of drug reduces the intake of large amounts of sugar?
Is it the one that also reduces the intake of large amounts of protein?
Fructose is blood sugar invisible, and plays no part in this conversation. Fructose can cause fatty liver and has been attributed with lots of voodoo, but the weird fructose focus of some is not evidence based. It's nonsense.
"The medical establishment and big pharma simple ignores the fact "
Do you really think the "medical establishment" hasn't been *screaming* about poor diets for decades? The fact that people ignored them doesn't give you an opening to suddenly spout horseshit. And big pharma has had an enormous focus on blood sugar for decades, and you're here yipping like they just want to sell you boner pills. What bizarre world is this?
> the "modern" high sugar diet that Kellogs introduced in the US and spread to the western world (even to Asia at some extent).
Kellogg? Did you know that white rice has a glycemic index significantly higher than table sugar (because, as previously mentioned, fructose is not a blood sugar)?
Yeah, a lot of people have bad diets, but infinitely more pressing is sedentary lifestyles. The reason Asia gets away with a rice-heavy diet (which is almost pure glucose, in a very simple form), though this is turning the wrong way, was busy, active lifestyles. The biological reality is that eating a big bowl of frosted flakes is perfectly fine if you follow it up with high amounts of activity.
Glucose is quite literally fuel for your body. And it's fine if you're actually using that fuel, but becomes a problem when often the overweight (and insulin resistant) and sedentary flood their blood with glucose, with nowhere for it to go.
> Fructose can cause fatty liver
It is also a large contributor to rising triglycerides levels and uric acid due to the way it is metabolized. Which in turn contributes to high blood pressure. It also makes Acetyl-CoA, which stimulates lipogenesis.
It is not even true that it is 'blood sugar invisible'. 30-50% of the fructose is converted in glucose and that's visible. The rest won't be available until you start burning fat.
> Yeah, a lot of people have bad diets, but infinitely more pressing is sedentary lifestyles.
No, that's only part of it. And a small part at that. The world didn't suddenly decide to get less active all of a sudden. You can blame some of the sedentary behaviors on societal changes (like suburbs and car dependency in the US), but other countries are getting just as unhealthy, metabolically speaking, and fat.
> The biological reality is that eating a big bowl of frosted flakes is perfectly fine if you follow it up with high amounts of activity.
It has to be really high. We are talking about hours to burn up that bowl of frosted flakes. Spend an hour at a treadmill, calculate the calories you spent. Now check the nearest cereal bar nutritional information. You'll be in for a surprise. You cannot outrun a bad diet.
Diet is most of what needs to be controlled for metabolic health. Resistance training will build muscles, and they are a good buffer since they will eat simple carbs even when you are inactive. Add cardio for cardiovascular health. But, unless you are an athlete or you are active the whole day, you should go easy on the frosted flakes.
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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.
Regarding “actual tests”: My team and I built a battery of longitudinal cognitive assessments useful for testing memory and brain function. (http://getNeuroUX.com)
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.
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.
GLP-1s have been used for over 20 years. There likely is enough data to say something, even if it's not water tight.
They've been used for over 20 years but until they became a weight loss drug recently, almost all of the research was on diabetics which introduces two confounding factors: diabetes and the diets diabetics already have to follow to manage the disease. It's hard to draw any conclusions when the results are muddied by those two factors.
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I’m not an expert on this, but haven’t GLP-1’s been used for quite a while on more limited scopes? So maybe there’s a cohort of people that could approach statistical significance.
IIRC, mostly used to help with type 2 diabetes... But effects on that cohort may not generalize to the general population.
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Cognitive Decline != Alzheimer's. There are other forms of cognitive decline in aging.
Much appreciated post, but can you keep the AI slop separate from the rest of it?
Which sort of affirms the mantra, "If you can't prove causation, try to prove correlation." This because you can market correlation to unsophisticated readers and imply causation.
> Which sort of affirms the mantra, "If you can't prove causation, try to prove correlation."
There’s already tons of correlation published for semaglutide lowering rates of dementia. This study is an effort at helping find the mechanism beyond the generally also known correlation that losing weight lowers rates of dementia.
Or, less conspiratorially, if correlation can be proven and causation is plausible but unproven, there may be benefits.
Proving correlation but not causation does NOT rule out causation.
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.
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?
Doesn’t socialized medicine mean that big brother already knows the answer to these questions? Why isn’t NHS or whomever more useful on these issues?
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