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.
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.
If the change has opened a harder question about someone's drinking, that belongs with a service rather than a thread.
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.