Semaglutide and MASH — March 2026

amsterdam_pete said:

The mechanism that matters here is not stomach emptying, it is central.

Pushing back on amsterdam_pete here. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.

If somebody has the primary source to hand I would rather cite it than paraphrase it.

One concrete data point for the thread. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

BethLabQueen said:

The trial means are being read too generously in this thread.

There is a second half to this that has not been said yet. 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.

Ask again with the specifics and you will get a better answer than this one.

A narrower follow-up, since the general answer is now clear:

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

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

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me. I was escalating because the number was available, not because I had stopped responding.