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#weight#semaglutide#glp#loss#more#risk#study#effects#dementia#inflammation
Discussion (74 Comments)Read Original on HackerNews
"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.
Many many times in US history we've said something is true, but put some big asterisks after them. Slavery is over (except it's definitely still permitted in the US), it's illegal to discriminate based on race (except we allowed redlining for generations and arguably are still fighting it), rape is illegal (unless it's your spouse, then it was legal until '93. And a lesser crime still in much of the country).
Voting is no different. Heck, one might argue we still don't have universal suffrage. People who want to vote but because we've put barriers like underfunding stations, long lines, not giving time off to vote, etc. we're clearly preventing some types of people.
This extra receptor is why Reta is a triple agonist unlike semaglutide (single glp1) or tirzepatide (glp1+gip double agonist).
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.
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.
Note I am not Western
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.
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.
Which to me just sounds like every other addictive drug. Paradise while you’re high, and eventually you pay for it.
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.
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)