De novo lipogenesis reduction on GLP-1 — anyone have experience?

FDA_TrackerJim said:

ALT was mildly raised at baseline, normalised at month five, and I now have no idea whether anything happened to the fibrosis that actually matters.

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.

amsterdam_pete said:

NASH/MAFLD therapeutic landscape and liver and MASH: GLP-1 agonists are emerging as potential first-line NASH therapy.

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.

FDA_TrackerJim said:

ALT was mildly raised at baseline, normalised at month five, and I now have no idea whether anything happened to the fibrosis that actually matters.

Adding a me-too, because a thread of one person's experience is not much use.

Clinical perspective, offered as context rather than as advice.

Liver imaging follow-up for liver and MASH: FibroScan at baseline showed CAP score 324 dB/m (moderate steatosis) and stiffness 8.8 kPa (possible fibrosis). Diagnosed with NAFLD.

After 10 months: CAP dropped to 227 dB/m (minimal steatosis) and stiffness normalized to 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.