Dr.PainCLE said:

Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

Worth separating that from liver and MASH, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

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

Worth separating that from liver and MASH, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

pete_manc_UK said:

I will push back on the "any working dose is fine" framing.

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.

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?

Reporting back.

Update. I did go to 2.4mg in the end, and the honest report is that it bought me less than the step before it and cost me two bad weeks. Worth knowing rather than worth repeating.