I understand not having a link to the primary source at the top of an article because you might be trying to write an explainer, but if you want to avoid confusing your readers but still do the right thing at the very least include a bunch of source links at the bottom of the article!

I know all the cynical reasons not to do it, but I feel like even the good faith objection has a pretty straightforward solution.

But but but we have to keep traffic on our website! Engagement!

That's why when you click on a link you see 1/10th of the article, and then a video, and 3 other irrelevant inlays for other links.

Oh and the video auto plays with sound.

And every word in the article that is remotely a 'tag' links to other parts of the website.

Will there be a large-dose trial? I imagine that’s going to be more difficult, as the weight-loss effect of GLP-1 means you cant include frail patients in your target group. And GLP-1 at high doses also has some unfavourable side-effects: nausea, vomiting, diarrhea, constipation.

For reference in typical maintenance doses:

- Rybelsus (type-2 diabetes; oral semaglutide 14 mg/day; much less bioavailability)

- Wegovy (obesity; injectable semaglutide 2.4 mg/wk)

- Ozempic (type-2 diabetes; injectable semaglutide 1.0 mg/wk)

Semaglutide (Ozempic) has potential therapeutic effects in neurodegenerative disorders through "modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis". It has shown benefits in animal models of Alzheimer's and Parkinson's. So they're not just testing a random drug, but something that could work.

For details, see: https://pubmed.ncbi.nlm.nih.gov/38921025

This diagram shows how Ozempic can produce these results, the various pathways from the GLP-1 receptor to reduce inflammation, protect neurons, and affect mitochondria: https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87c0/11202139/72234dd...

"Type 3 diabetes" is one of the speculated causes of alzheimer's. The evidence there is not great.

I know we can tell that a chemical does a particular thing in the body, but can we tell that it does not do anything other than that thing? The body is ridiculously complex, and as far as I know we don’t know how every part (or combination of parts) works.

Edit: I mean in the theoretical “this targets the x receptor” kind of way, not in “we tested this and found no causal link” way.

As I understand it, one of the reasons GLP-1 agonists seem to affect so many different things is that evolutionarily, it does not seem at all surprising that a huge number of things are hooked on the hungry/full signal.

I kind of think if it fixes a fundamental issue - too much weight.

Another problem it seems to help with is addictive/impulsive behavior. This might lead to wrong choices in diet or activity.

I suspect that many many functions of the body are degraded or disabled by too much weight or wrong choices, and fixing those problems might let the body cure and maintain itself properly.

A lot of medical research is "x is correlated with y and we have no idea why".

Maybe because poor diet has been linked to alzheimers?

It was correlated to lower Dementia rates in a past study. https://journals.sagepub.com/doi/10.1177/13872877251351329

The article describes data showing a correlation between Ozempic use and slowed progression of certain brain conditions. The study aimed to determine whether that effect came from Ozempic itself or simply from weight loss. Once researchers controlled for weight loss, the effect disappeared. In other words, correlation, not causation.

I read this[1] some time ago. Seems relevant now.

- [1] https://www.astralcodexten.com/p/why-does-ozempic-cure-all-d...

"Alleged magic cure does not solve all our problems" just isn't as catchy.

It's disappointing to the manufacturers and consumers because many boomers are taking it already to treat 40+ years of poor and/or indulgent consumption (and more will now that they've negotiated a price reduction).

Glp-1 drugs inhibit drinking and compulsive behaviors and I'm not sure the mechanism of action is known

We already know that's not the case though. A huge portion of the benefits are downstream of obesity, yes, but we already know GLPs have positive effects even without weight loss.

It is a reasonable thought, but that exact question has been investigated and benefits were not totally explained by weight loss. I don't recall the link, but it was featured on HN

>eventually all of the additional positives of the drug will resolve to obesity is bad and reducing obesity has health benefits.

This is not true.

Ozempic appears to affect the brain's rewards system and its known to decreased cravings and urges for a range of unhealthy behaviors, from alcohol consumption and smoking to gambling and shopping to nail biting and skin picking.

Beyond that, Ozempic appears to lower the risk of heart attacks and strokes in overweight people well beyond what weight loss alone would explain. Maybe due to the above (less drinking and smoking) or another unknown mechanism of action.

https://www.scientificamerican.com/article/weight-loss-drug-...

Nah, obesity reduction is itself a downstream effect of messing with neurotransmitters. There have to be other consequences of that - both good and bad.