Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
So the question, as narrowly as I can put it: whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. I would rather have one careful answer than five confident ones.
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.
BiostatsBrad 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.
BiostatsBrad 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.
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Shop Reference Standardssarah.morrison said:NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.
Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 11 months on GLP-1 therapy:
| Marker | Baseline | Current | Normal Range |
|---|---|---|---|
| ALT | 65 | 27 | 7-56 U/L |
| AST | 53 | 21 | 10-40 U/L |
| GGT | 70 | 33 | 9-48 U/L |
| ALP | 100 | 77 | 44-147 U/L |
FibroScan also improved — liver stiffness from 10.5 kPa to 6.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.
anders_CPH said:Liver ultrasound comparison for liver and MASH: my hepatologist ordered serial ultrasounds to track NAFLD regression.
Adding a me-too, because a thread of one person's experience is not much use.