LarryQC_SD said:Steady state is the thing most people miss.
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.
I would rather be corrected than agreed with, if it comes to it.
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.
LibrarianMeg said:I will push back on the "any working dose is fine" framing.
Coming at LibrarianMeg’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.
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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
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Shop Reference StandardsOne thing that is still open after ben_calgary’s answer:
Whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is?
Closing the loop on my own question.
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.