Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. It is about liver and MASH, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
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.
The practical version
With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most threads assume.
What I am not sure about
So the question, as narrowly as I can put it: whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Tell me what I have not thought of.
— james_edin · corrections welcome and will be edited into this post with credit