JennaRN said:The dose-response is real but shallow at the top.
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.
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.
I would rather be corrected than agreed with, if it comes to it.
PurityPaulOR 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.
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Shop Reference StandardsOne thing that is still open after hans_munich’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. 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.