genuine question about dual agonist that I am slightly embarrassed to ask
Slightly embarrassed to be asking this, but: genuine question about dual agonist that I am slightly embarrassed to ask.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
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.
Happy to answer the boring questions. Those are usually the ones worth asking.
best — the order this archive was captured in
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.
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.
independent testing on this compound is very thin
The honest evidence position, written out so this board does not drift.
Adding the standing caveat — unapproved compound, research material is not for human use.
Bought small because the evidence base is early. That is the only defensible position I could construct.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
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.
Has anyone posted an independent purity result for this compound?
fibrosis improvement without worsening steatohepatitis is the phrase to learn
read the histology endpoint definitions before quoting a response rate
Removed the escalation schedule. Unapproved compound, no protocols for other members, no exceptions.
Are you reading the publication or a summary?
Are you reading the publication or a summary?
renzo_asante is right that biopsy and imaging endpoints are not interchangeable.
Are you reading the publication or a summary?
This is the framing the board needs. It is a hepatic programme first.
this board is small because the compound is early
This. Biopsy-confirmed and imaging-suggested are different evidentiary categories and get run together constantly.
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Right, and the trial titration was slow for reasons that are visible in the tolerability tables.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
That figure is from the obesity programme, and this thread is about the hepatic one.
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.
research material is not approved for human use, which is why the clinical record here is thin
research material is not approved for human use, which is why the clinical record here is thin
Disagreeing with this bit: that number comes from a different programme with a different population.
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
glucagon agonism and energy expenditure is the mechanistic thread
the weight numbers are secondary to what this is being developed for
Agreed.
Agreed — and the endpoint definitions are where the actual claim lives.
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.
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
MASH endpoints are histological, which is a much harder bar
- 1Agreed. The hepatic programme is the point of this compound and the weight…9 comments in this branch · started by u/customs_seizure_sid
- 2read the histology endpoint definitions before quoting a response rate7 comments in this branch · started by u/farid_kuipers