why does nobody talk about dual agonist
why does nobody talk about dual agonist, and I want the answer with the reasoning attached rather than just the conclusion.
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Sceptical readings welcome. The confident ones are the ones I distrust.
best — the order this archive was captured in
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.
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Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
research material is not approved for human use, which is why the clinical record here is thin
phase 2 in liver disease is a different evidence question from weight
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.
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
do not import intuitions from the obesity programmes
That figure is from the obesity programme, and this thread is about the hepatic one.
Correcting myself: the readout I quoted was the 42-week interim rather than the endpoint.
read the histology endpoint definitions before quoting a response rate
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.
the titration in the trials was slow and deliberate
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
this board is small because the compound is early
That is an escalation schedule for an unapproved compound and this board does not host those.
That is an escalation schedule for an unapproved compound and this board does not host those.
Adding the standing caveat — unapproved compound, research material is not for human use.
independent testing on this compound is very thin
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Yes — histological endpoints are a far harder bar than the surrogate measures people are used to quoting.
MASH endpoints are histological, which is a much harder bar
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.
Push back: the evidence here is phase 2, in a specific population, and it does not support a general ranking.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
- 1phase 2 in liver disease is a different evidence question from weight14 comments in this branch · started by u/titration_marshal