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ForumsMASH / Liver DiseaseAlcohol + MASH + GLP-1 — need advice

Alcohol + MASH + GLP-1 — need advice

sarah_nash92 Wed, Jun 26, 2024 at 11:40 AM 12 replies 1,927 viewsPage 1 of 3
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sarah_nash92
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Jun 26, 2024 at 11:40 AM#1

Writing this once so I can stop repeating it across threads. 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 I am trying to establish is whether the change in tolerance is the smaller stomach, the smaller body, or something central, and whether it settles. Tell me what I have not thought of.

— sarah_nash92 · corrections welcome and will be edited into this post with credit
36 6NauseaFreeNow, SteveThurs, B12Beth and 33 others
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LarryQC_SD
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Jun 26, 2024 at 12:20 PM#2
sarah_nash92 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.

I would rather be corrected than agreed with, if it comes to it.

35 5paul_denver, TinaHashiRN, robert_kc and 32 others
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Dr.MetabolicMD
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Jun 26, 2024 at 1:00 PM#3
sarah_nash92 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 read this differently from sarah_nash92, on substance rather than tone. This treats a plausible mechanism as a demonstrated one. Plausible is where you start looking, not where you stop.

34 4HealthEcon_DC, PedsEndoPhilly, SleepDoc_PDX and 31 others
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james_edin
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Jun 26, 2024 at 1:40 PM#4

This one has a reasonably settled answer, so here it is. 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.

33 3oliver_london, tane_welly, Dr.PathRoch and 30 others
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rick_sfbay
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Jun 26, 2024 at 5:21 PM#5
LarryQC_SD said:
Agreed, and ALT falling is not the same as fibrosis improving.

This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.

32 2Dr.BariatricHTX, LindaRN_retired, tommy_boulder and 29 others
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