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MPSimmonsyesterday at 7:02 PM8 repliesview on HN

At what point do we start to re-evaluate and re-test old assumptions about how much weight/caloric restriction impacts things? It seems unlikely that a molecule that slots into receptors in the pancreas also does something(?) to cardiac muscle [1], addiction [2], and now osteoarthritis(!).

This feels like a stretch to say that this happens independent of weight loss, and much more like we may have underestimated the impacts of weight loss on all of these other facets of life.

[1] - https://pmc.ncbi.nlm.nih.gov/articles/PMC12431743/

[2] - https://med.stanford.edu/news/insights/2025/04/ozempic-addic...


Replies

rustyhancockyesterday at 7:16 PM

Similar reports have been ongoing about Metformin (another medication used for diabetes that causes weight loss and improves metabolic profile).

It's the simplest explanation that we have been underestimating just how unhealthy we are?

There's a synergy here, eat healthier, reduce blood sugar spikes, lose weight. And you are healthier than each individual effect alone would cause.

Maybe we're just ruining our bodies even if we don't put on weight by eating sugary foods that spoke our blood sugar. Or big meals that constantly make us switch into sit down and digest mode.

I'm open to something more happening but this isn't just GLPs. It seems we have uniquely attacked our bodies in a way that diabetes is the ultimate result but the entire journey is exquisitely toxic to our physiology.

Maybe fasting helps. Maybe keto helps. But this is similar to people who live off McDonalds suddenly go vegan and become healthy, is veganism that great? Or was the alternative for you just so awful for you?

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kixiQuyesterday at 7:10 PM

FTFA:

> By designing a precise diet-controlled setting to rule out the effect of appetite suppression and weight loss induced by SG, we demonstrate a weight loss-independent mechanism.

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estearumyesterday at 7:10 PM

Hormones do a lot all over your body.

You're commenting on a paper that specifically found OA improvement without weight loss improvement...

RobotToasteryesterday at 7:10 PM

There's GLP-1 receptors in the brain, they induce neurogenesis

FeteCommunisteyesterday at 7:15 PM

> addition [2]

I had heard about the effects on addiction but this typo had me thinking there might be some effect on arithmetic ability, too.

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cthalupayesterday at 7:28 PM

If they're not losing weight they're not restricting calories. Energy has to come from somewhere.

They explicitly controlled for all of this.

MattGaiseryesterday at 7:09 PM

Why is that unlikely?

There are other known molecules that are many to many like cortisol, testosterone, and insulin.

pertymcpertyesterday at 7:10 PM

I mean...if you read the paper they control for that.