Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.
Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
What I am after is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Practical detail welcome, however dull — the duller the better.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
Dr.PathRoch said:The liver data is among the strongest non-weight findings in the class.
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.
[1] Newsome PN, et al. N Engl J Med. 2021;384(12):1113-1124.
Dr.PathRoch said:The liver data is among the strongest non-weight findings in the class.
Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.
Baseline: "Moderate hepatic steatosis, liver span 17.2cm, echogenic texture consistent with fat infiltration"
Month 8: "Mild steatosis, liver span 15.8cm, improved echogenicity"
Month 14: "Minimal to no steatosis, normal liver span 14.5cm, normal echotexture"
My liver literally shrank and de-fattened. The ultrasound tech said she's seen this pattern increasingly in GLP-1 patients and it's remarkable how consistently the fatty liver resolves.
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Shop Reference StandardsLabKate said:Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.
Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 8 months on GLP-1 therapy:
| Marker | Baseline | Current | Normal Range |
|---|---|---|---|
| ALT | 73 | 30 | 7-56 U/L |
| AST | 56 | 24 | 10-40 U/L |
| GGT | 73 | 36 | 9-48 U/L |
| ALP | 103 | 80 | 44-147 U/L |
FibroScan also improved — liver stiffness from 10.5 kPa to 5.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.
kate.chem said:NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.
Same experience, arrived at from the opposite direction. I had assumed I was the exception until I read this.