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 narrow version of the question is whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Happy to be told the question itself is wrong.
MASHdoc_SA 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.
MASHdoc_SA 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 314 dB/m (moderate steatosis) and stiffness 10.8 kPa (possible fibrosis). Diagnosed with NAFLD.
After 12 months: CAP dropped to 237 dB/m (minimal steatosis) and stiffness normalized to 5 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 StandardsDr.BariatricHTX said:Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 314 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.
MikeFit_NJ said:NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.
Mine went the same way, slower. The detail I would add is minor and it is already implied above.