Semaglutide linked to 26% lower 5-year predicted dementia risk

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.

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.

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 […]

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 weigh […]

This is interesting. Diabetes is a well-known risk factor for dementia.

Isn't lower calorie consumption in general correlated to longevity? (Assuming no major malnutrition)

Better summary:

Two years of semaglutide treatment appears to substantially slow the worsening of a blood protein signature associated with future dementia risk

That's a big percent for something that is completely devastating. This is objectively good 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.