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ForumsMASH / Liver DiseaseDe novo lipogenesis reduction on GLP-1 — anyone have experience? Page 2

De novo lipogenesis reduction on GLP-1 — anyone have experience?

FDA_TrackerJim Tue, May 6, 2025 at 7:57 PM 7 replies 1,424 viewsPage 2 of 2
Dr.SurgeonPGH
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May 6, 2025 at 11:37 PM#6
MikeFit_NJ said:
Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.

NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy. The Phase 2b data for semaglutide showed 59% NASH resolution (vs 17% placebo) with 43% achieving fibrosis improvement[1].

Mechanism: GLP-1R activation reduces hepatic lipogenesis, increases fatty acid oxidation, reduces hepatic inflammation, and may directly reduce hepatic stellate cell activation (fibrosis pathway).

With resmetirom (thyroid hormone receptor agonist) recently approved for NASH, the field is evolving rapidly. Combination approaches (GLP-1 + resmetirom) are being explored.

References:
[1] Newsome PN, et al. N Engl J Med. 2021;384(12):1113-1124.
47 17DoseLogDan, SleepFixSam, PurityPaulOR and 44 others
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kate.chem
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May 7, 2025 at 1:03 AM#7
FDA_TrackerJim said:
Fatty liver on an incidental scan two years ago and nobody followed it up.

Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 6 months on GLP-1 therapy:

MarkerBaselineCurrentNormal Range
ALT66287-56 U/L
AST642410-40 U/L
GGT71289-48 U/L
ALP1117844-147 U/L

FibroScan also improved — liver stiffness from 8.5 kPa to 5.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.

46 16VanRx_Mike, steve_okc, dave_SLC and 43 others
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MASHdoc_SA
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May 7, 2025 at 2:29 AM#8
Dr.SurgeonPGH said:
NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.

There is a second half to this that has not been said yet. Worth answering the question that was asked rather than the one behind it. The narrow version usually has an answer; the broad version usually does not, and answering the broad one is how a thread stops being useful.

45 15JennaRN, LabKate, kate.chem and 42 others
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nick_newbie
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May 7, 2025 at 3:55 AM#9

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

What did you change at the same time, and can you separate the two now?

44 14LarryQC_SD, wanda_boise, NurseAsh_DET and 41 others
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FDA_TrackerJim
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May 7, 2025 at 10:48 AM#10

Closing the loop on my own question.

Closing this out. What actually changed my mind was the point about waiting for a trend instead of reading a single measurement, which is embarrassing in hindsight and worth saying anyway.

Last edited: May 7, 2025 at 1:48 PM
12 10jason_paloalto, Dr.LeslieOBGYN, MikeNYC_runner and 9 others
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