4 months in and hepatic fat is still the thing I get wrong
4 months in and hepatic fat is still the thing I get wrong, logged the same way every week so the comparison is at least internally fair.
The numbers the title promised, since a headline without them is worthless: 4 months. Everything below is context for those.
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.
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.
Sceptical readings welcome. The confident ones are the ones I distrust.
best — the order this archive was captured in
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.
The escalation schedules in the published protocols are slow and deliberate, and the tolerability tables show why.
Agreed — and the endpoint definitions are where the actual claim lives.
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Sent a vial to Medutest because there was nothing on file. 99.2% against a claimed 98.5%. First entry for this compound in my own log.
this board is small because the compound is early
Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.
Agreed that the endpoint definitions matter enormously and almost nobody reads them before quoting a response rate.
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 titration in the trials was slow and deliberate
Biopsy-confirmed population or imaging-selected?
Which phase and which arm are you quoting?
Removed the escalation schedule. Unapproved compound, no protocols for other members, no exceptions.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
This is the framing the board needs. It is a hepatic programme first.
This. Biopsy-confirmed and imaging-suggested are different evidentiary categories and get run together constantly.
Are you reading the publication or a summary?
Push back: the evidence here is phase 2, in a specific population, and it does not support a general ranking.
the weight numbers are secondary to what this is being developed for
That is an escalation schedule for an unapproved compound and this board does not host those.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.
fibrosis improvement without worsening steatohepatitis is the phrase to learn
Careful with the mechanism claim. Glucagon agonism is plausible as an explanation and it has not been isolated as the operative one.
Yes — histological endpoints are a far harder bar than the surrogate measures people are used to quoting.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
Careful with the mechanism claim.
Disagreeing with this bit: that number comes from a different programme with a different population.
Same. Very thin independent data on this one, which should make everybody here more tentative than they are.
- 1the weight numbers are secondary to what this is being developed for10 comments in this branch · started by u/valeria_karlsen
- 2Agreed that the endpoint definitions matter enormously and almost nobody…6 comments in this branch · started by u/kaia_wojcik