Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. It is about alcohol, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
Reduced interest in alcohol is one of the most consistently reported off-target effects, and the mechanism is plausibly the same reward-salience pathway that quiets food noise. The practical part people get wrong is that tolerance changes: less food in the stomach, faster gastric emptying of liquid relative to solids, and a smaller body mean the same two drinks land considerably harder than they used to.
The condition it depends on
If the change has opened a harder question about someone's drinking, that belongs with a service rather than a thread.
What I am not sure about
What would genuinely help is knowing whether the change in tolerance is the smaller stomach, the smaller body, or something central, and whether it settles. Practical detail welcome, however dull — the duller the better.
DanielChem_CHI said:Reduced interest in alcohol is one of the most consistently reported off-target effects, and the mechanism is plausibly the same reward-salience…
Agreed, and ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.
DanielChem_CHI said:Reduced interest in alcohol is one of the most consistently reported off-target effects, and the mechanism is plausibly the same reward-salience…
I do not accept the framing. The question has been narrowed to the version that has a tidy answer, and the part that was dropped is the part the OP actually asked about.
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Browse GL BiochemShort answer first, then the reasoning. The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.
KevinCompounds said:Agreed, and ALT falling is not the same as fibrosis improving.
Can confirm. Same sequence, different timescale.