Answering the narrow version, because the broad one does not have a single answer. 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.

Dr.NateNeph said:

The liver data is among the strongest non-weight findings in the class.

That is correct as far as it goes, and here is where it stops going. Orforglipron is a small molecule rather than a peptide, which is the whole point: no SNAC absorption enhancer, no fasting window, no cold chain, and oral bioavailability in the tens of percent instead of around one. Phase 2 put it near 14.7% weight loss at 36 weeks on the top dose with a side-effect profile that looks like the injectables.

NicoleRaleigh said:

I have been following the oral non-peptide data since phase 2 and I am trying to work out how much of the enthusiasm here is about efficacy and how…

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.

From the other side of the consultation, briefly. Take it one variable at a time. Almost every unanswerable question in these threads is unanswerable because three things changed in the same fortnight, and no amount of subsequent argument can untangle them after the fact.