[Discussion] small community, high signal, let us keep it that way
small community, high signal, let us keep it that way. Change my mind, genuinely — I have no stake in being right about this.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
best — the order this archive was captured in
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.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
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Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
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.
What does the tolerability table say at that dose?
the titration in the trials was slow and deliberate
biopsy-confirmed is not the same as imaging-suggested
Histological endpoints in this field are scored on biopsy: resolution of steatohepatitis without worsening of fibrosis, or improvement in fibrosis without worsening of steatohepatitis. Both are harder to achieve and to interpret than an imaging surrogate.
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.
What does the tolerability table say at that dose?
This is the framing the board needs. It is a hepatic programme first.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
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