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ForumsMASH / Liver DiseaseSemaglutide and MASH — liver fat reduction quantification Page 2

Semaglutide and MASH — liver fat reduction quantification

MASHdoc_SA Mon, Jun 8, 2026 at 3:08 PM 13 replies 146 viewsPage 2 of 3
hank_denver
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Jun 8, 2026 at 4:45 PM#6

The figures, for anyone assembling their own picture. 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.

48 18ingrid_STO, pete_nash, hank_denver and 45 others
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quinn_sf
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Jun 8, 2026 at 5:24 PM#7

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

What the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss?

47 17Dr.PathRoch, mona_PHX, andrew_nyc and 44 others
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Dr.CardioMD
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Jun 8, 2026 at 6:03 PM#8
hank_denver said:
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…

There is a second half to this that has not been said yet. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

Last edited: Jun 9, 2026 at 12:03 AM
46 16tony_orlando, Dr.NephBHM_UK, kim_atl_prep and 43 others
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MASHdoc_SA
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Jun 8, 2026 at 6:42 PM#9

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.

Last edited: Jun 8, 2026 at 9:42 PM
45 15LabKate, kate.chem, DataDave and 42 others
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mike_mealprep
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Jun 8, 2026 at 9:50 PM#10
Dr.CardioMD said:
The mechanism that matters here is not stomach emptying, it is central.

That is correct as far as it goes, and here is where it stops going. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.

7 5sophie_paris, mel_PDX, Dr.AddMedPHL and 4 others
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