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ForumsMASH / Liver DiseaseSemaglutide and MASH — what worked for you?

Semaglutide and MASH — what worked for you?

PharmHunterJen Thu, Aug 7, 2025 at 5:42 AM 12 replies 1,442 viewsPage 1 of 3
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PharmHunterJen
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Aug 7, 2025 at 5:42 AM#1

Started at 0.25mg with a fairly bad first week, held each step the full four weeks, and I am now at 1mg with no side effects worth naming.

So the question, as narrowly as I can put it: whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg.

Happy to be told the question itself is wrong.

35 5Dr.LipidDallas, alex_tucson, kevin_tulsa and 32 others
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JennaRN
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Aug 7, 2025 at 7:13 AM#2

This one has a reasonably settled answer, so here it is. Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.

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

34 4PeptideSynthNJ, Dr.KarenChen, Dr.NateNeph and 31 others
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Dr.EndoIndy
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Aug 7, 2025 at 8:44 AM#3
JennaRN said:
Steady state is the thing most people miss.

That is correct as far as it goes, and here is where it stops going. 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.

33 3marcus_mpls, DeniseRN_TPA, SandraNC_45 and 30 others
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kim_atl_prep
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Aug 7, 2025 at 10:15 AM#4
PharmHunterJen said:
Started at 0.25mg with a fairly bad first week, held each step the full four weeks, and I am now at 1mg with no side effects worth naming.

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.

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Dr.EndoEP
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Aug 7, 2025 at 7:09 PM#5

Adding the clinical framing, because it changes how the question reads.

PharmHunterJen said:
...but the FDA says semaglutide...

Interesting point. I want to add some regulatory nuance: the FDA labeling reflects the specific clinical trial data submitted for approval. Real-world clinical practice often extends beyond the FDA label based on emerging evidence and clinical judgment.

Example: semaglutide was first approved for diabetes (Ozempic), then obesity (Wegovy). The molecule didn't change — our understanding of its applications expanded. Similarly, semaglutide may evolve as more data accumulates.

31 1LindaRN_retired, tommy_boulder, hyun_seoul and 28 others
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