A reference post rather than a discussion. Corrections are the point; I would rather this be right than mine. It is about liver and MASH, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.
The practical version
With resmetirom now available for MASH, combination approaches are being explored, so the standard of care in this area is moving faster than most threads assume.
What I am not sure about
The question I want answered is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Numbers rather than impressions, if you have them.
Dr.GastroMayo said:The liver data is among the strongest non-weight findings in the class.
ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase 3 ATTAIN trial. NASH resolution was achieved in ~60% of patients[1].
This is relevant to liver and MASH because survodutide's glucagon agonism specifically targets hepatic lipid metabolism — making it potentially the best-in-class agent for NASH/MAFLD comorbid with obesity.
[1] Sanyal AJ, et al. N Engl J Med. 2024.
Dr.GastroMayo said:The liver data is among the strongest non-weight findings in the class.
Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD). After 10 months on GLP-1 therapy:
| Marker | Baseline | Current | Normal Range |
|---|---|---|---|
| ALT | 75 | 22 | 7-56 U/L |
| AST | 48 | 24 | 10-40 U/L |
| GGT | 75 | 32 | 9-48 U/L |
| ALP | 95 | 82 | 44-147 U/L |
FibroScan also improved — liver stiffness from 9.5 kPa to 5.2 kPa. The evidence for GLP-1 agonists in NAFLD/NASH is very promising.
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Browse GL BiochemDr.KarenChen said:Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD).
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.CardioMD said:ATTAIN trial (survodutide) context for liver and MASH: survodutide, a GLP-1/glucagon dual agonist, showed -18.7% body weight at 46 weeks in the Phase…
This is my experience too, for whatever a second data point is worth. I had assumed I was the exception until I read this.