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ForumsMASH / Liver DiseaseLiver biopsy changes on semaglutide — 6 month update

Liver biopsy changes on semaglutide — 6 month update

jim_asheville Mon, Dec 22, 2025 at 12:21 AM 13 replies 1,087 viewsPage 1 of 3
jim_asheville
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Dec 22, 2025 at 12:21 AM#1

I moved from brand to compounded semaglutide at the same nominal dose and cannot decide whether what changed is the material, my titration, or my expectations.

So the question, as narrowly as I can put it: what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss.

Tell me what I have not thought of.

42 12MikeKY_noInsulin, Dr.RaviCardio, jennifer_SEA and 39 others
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VendorMark
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Dec 22, 2025 at 12:34 AM#2

Answering the narrow version, because the broad one does not have a single answer. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

Last edited: Dec 22, 2025 at 2:34 AM
41 11KristenIndy, MarkLI_maint, Dr.PeteFamMed and 38 others
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lucas_SP_BR
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Dec 22, 2025 at 12:47 AM#3
VendorMark said:
The dose-response is real but shallow at the top.

Agreeing with VendorMark, and the qualification matters more than the agreement. 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.

Last edited: Dec 22, 2025 at 2:47 AM
40 10zoe_NC, Dr.ObesityLA, NurseKim_ATL and 37 others
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hannah_MT
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Dec 22, 2025 at 1:00 AM#4
jim_asheville said:
I moved from brand to compounded semaglutide at the same nominal dose and cannot decide whether what changed is the material, my titration, or my…

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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PeptideChemSF
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Dec 22, 2025 at 2:08 AM#5

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

jim_asheville 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.

Last edited: Dec 22, 2025 at 6:08 AM
38 8BrianDallas92, labquiet_amy, emily_PDX and 35 others
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