small win: glucagon stopped being a problem at week 36
small win: glucagon stopped being a problem at week 36. This is a description of what happened to me and not a plan for anybody else.
The endpoint vocabulary, because you cannot read this literature without it.
Resolution of steatohepatitis without worsening of fibrosis and improvement in fibrosis without worsening of steatohepatitis are the two standard composite endpoints, both scored on biopsy by pathologists against a defined system. Liver fat fraction is an imaging surrogate that correlates imperfectly with histology.
A trial can move the surrogate substantially and the histological endpoint modestly. Both results are real; they answer different questions. Anybody quoting a response rate here should say which endpoint it refers to, and most summaries do not.
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.
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
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
a liver endpoint is not a weight endpoint with better marketing
Left up. It reads the paper carefully and is explicit about the population.
not approved anywhere, and the boards forget that constantly
the weight numbers are secondary to what this is being developed for
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
Same. Very thin independent data on this one, which should make everybody here more tentative than they are.
Same.
hugo_bergstrom is right that biopsy and imaging endpoints are not interchangeable.
The honest evidence position, written out so this board does not drift.
Phase 2 data exists in a specific, biopsy-characterised population, with a slow protocol escalation and tolerability tables worth reading in full. Nothing containing this compound is approved by any regulator anywhere. Research-use-only material is not approved for human use.
Independent purity results across this entire site number in the low single figures. That means nobody here — including the people who post most confidently — has a basis for statements about batch-to-batch consistency. If you test something, post it; the log is the only thing that will change that position.
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.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
That is an escalation schedule for an unapproved compound and this board does not host those.
Has anyone posted an independent purity result for this compound?
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
What does the tolerability table say at that dose?
Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.
Not convinced.
Adding the standing caveat — unapproved compound, research material is not for human use.
Which phase and which arm are you quoting?
Which phase and which arm are you quoting?
This is the framing the board needs. It is a hepatic programme first.
Is that a weight number from a different programme?
independent testing on this compound is very thin