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c/survodutide·posted 1 year ago by u/lyophile_lou

4 months in and MASH is still the thing I get wrong

Caution Well Actually ×5

4 months in and MASH is still the thing I get wrong. Numbers below. Ask me the boring questions, they are the useful ones.

Numbers, in the order they matter: 4 months.

What this compound is actually being developed for, since the boards treat it as a weight-loss molecule with a footnote.

It is a dual GLP-1 and glucagon receptor agonist, and the glucagon arm links to hepatic fat and energy expenditure. The headline programme is metabolic liver disease, with endpoints scored on biopsy rather than on a scale.

That matters for how the data should be read. A histological response rate in a biopsy-confirmed population answers a very different question from a mean weight change in an obesity trial, and quoting one in place of the other — which happens in nearly every thread here — is not a comparison.

Bought small because the evidence base is early. That is the only defensible position I could construct.

Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.

820 up / 170 down83% upvoted14 commentsid 1tlepa5 Jan 2025

14 comments

11 in this archive, depth 3

best — the order this archive was captured in

u/cold_chromatogram_only87 points·1 year ago

Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.

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[deleted]34 points·1 year ago

[deleted]

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u/mod_cold_roommod · c/coldchain16 points·1 year ago

That figure is from the obesity programme, and this thread is about the hepatic one.

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u/camila_marchand54 points·1 year ago

It is a dual agonist at the GLP-1 and glucagon receptors. The glucagon arm is associated with increased energy expenditure and with effects on hepatic fat, which is why the development programme is oriented towards liver disease.

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u/crosspost_bot_no0 points·1 year ago

Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.

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u/paper_trail_paulavetting1 point·1 year ago

Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.

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u/hana_lehtinen1 point·1 year ago

Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.

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u/mod_cold_roommod · c/coldchain1 point·1 year ago·edited

Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.

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u/samir_falk19 points·1 year ago

fibrosis improvement without worsening steatohepatitis is the phrase to learn

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u/hugo_bergstrom14 points·1 year ago

Sent a vial to Medutest because there was nothing on file. 99.6% against a claimed 99.0%. First entry for this compound in my own log.

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u/tomas_lokken3 points·1 year ago·edited

Spent an evening on the histology scoring system and understood the trial literature far better afterwards.

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About c/survodutide

Survodutide-specific discussion: glucagon-receptor co-agonism, the hepatic fat and MASH resolution data, and how the side-effect profile compares with GIP-based dual agonism. Small community, high signal.

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