why does nobody talk about MASH
why does nobody talk about MASH, and I want the answer with the reasoning attached rather than just the conclusion.
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.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
The escalation schedules in the published protocols are slow and deliberate, and the tolerability tables show why. That is a description of the trials rather than a suggestion for anybody.
Careful with the mechanism claim. Glucagon agonism is plausible as an explanation and it has not been isolated as the operative one.
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
This is the framing the board needs. It is a hepatic programme first.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost no
Disagreeing with this bit: that number comes from a different programme with a different population.
Yes — nothing containing this is approved anywhere, which is the first fact and usually the last one mentioned.
Biopsy-confirmed population or imaging-selected?
the titration in the trials was slow and deliberate
How fast was the escalation in that protocol?
Has anyone posted an independent purity result for this compound?
Sent a vial to Janoshik because there was nothing on file. 99.5% against a claimed 99.0%. First entry for this compound in my own log.
independent testing on this compound is very thin
Is that a weight number from a different programme?
phase 2 in liver disease is a different evidence question from weight
the weight numbers are secondary to what this is being developed for
Phase 2 in a biopsy-confirmed population is a demanding design: recruitment is slow, the population is specific, and the results do not generalise to people who have not been characterised that way.
Independent result logged. There are almost none for this compound, so it is genuinely valuable.
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.
Right, and the trial titration was slow for reasons that are visible in the tolerability tables.
Push back: the evidence here is phase 2, in a specific population, and it does not support a general ranking.
MASH endpoints are histological, which is a much harder bar
fibrosis improvement without worsening steatohepatitis is the phrase to learn
This. Biopsy-confirmed and imaging-suggested are different evidentiary categories and get run together constantly.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
That figure is from the obesity programme, and this thread is about the hepatic one.
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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