Adding the numbers, since they settle part of this. 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.

One thing that is still open after DebRD_ATL’s answer:

Whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is?

josh_phd_bmore said:

With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most…

Coming at josh_phd_bmore’s question from a different direction. 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.

OP back with an update, since a thread like this is useless without one.

Update — my curve sits below the published mean and the explanation is that the trial arm had support I do not have. That was reassuring rather than otherwise.

SarahChen_PharmD said:

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

Propensity score matching studies and the trial evidence: when RCTs aren't available for a specific question, propensity score-matched observational studies can provide useful evidence.

A recent PSM study of 12,000 GLP-1 users vs matched controls showed reduced heart failure hospitalization (HR 0.74) over 3 years of follow-up[1].

These results complement the RCT data and suggest the benefits translate to real-world populations.