Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. 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
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. Tell me what I have not thought of.
james_edin 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 6 months on GLP-1 therapy:
| Marker | Baseline | Current | Normal Range |
|---|---|---|---|
| ALT | 67 | 24 | 7-56 U/L |
| AST | 50 | 22 | 10-40 U/L |
| GGT | 77 | 34 | 9-48 U/L |
| ALP | 97 | 84 | 44-147 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.
james_edin said:The liver data is among the strongest non-weight findings in the class.
Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 335 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible fibrosis). Diagnosed with NAFLD.
After 15 months: CAP dropped to 228 dB/m (minimal steatosis) and stiffness normalized to 5.6 kPa. Hepatologist says the liver is essentially healing itself as the metabolic stress resolves.
GLP-1 agonists may become first-line NASH therapy. The Phase 3 data on semaglutide for NASH is very promising.
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Shop Reference Standardsanders_CPH said:Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 335 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible…
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.RenalNash said:Liver enzyme update related to liver and MASH: I had mildly elevated ALT/AST at baseline (likely NAFLD).
Adding a me-too, because a thread of one person's experience is not much use.