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ForumsMASH / Liver DiseaseSemaglutide and MASH — March 2026

Semaglutide and MASH — March 2026

sophie_paris Tue, Dec 17, 2024 at 7:15 PM 42 replies 2,138 viewsPage 1 of 9
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sophie_paris
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Dec 17, 2024 at 7:15 PM#1

Six months in at 2.4mg. The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the tail rather than the headline.

The bit I cannot resolve on my own is how much of the between-person variation is pharmacokinetic and how much is just adherence measured badly.

Tell me what I have not thought of.

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Dr.GastroMayo
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Dec 17, 2024 at 7:34 PM#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".

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mona_PHX
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Dec 17, 2024 at 7:53 PM#3
Dr.GastroMayo said:
The dose-response is real but shallow at the top.

Dr.GastroMayo has the substance of this right. The condition it depends on is worth stating. 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.

Correct me if the detail matters more than I have assumed.

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TomTeleRx
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Dec 17, 2024 at 8:12 PM#4
sophie_paris said:
The first four months were close to the trial curve and the last two have been flat, which is roughly what the STEP 1 figure predicts if you read the…

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

Happy to go further on any of that.

Last edited: Dec 17, 2024 at 9:12 PM
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Dr.KarenChen
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Dec 17, 2024 at 9:52 PM#5

Clinical perspective, offered as context rather than as advice.

sophie_paris 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.

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