glucagon is the most under-discussed thing on this board
Something I keep coming back to: glucagon is the most under-discussed thing on this board.
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.
Would rather be corrected in public than confident in private.
best — the order this archive was captured in
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.
Left up. It reads the paper carefully and is explicit about the population.
What does the tolerability table say at that dose?
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.
Which endpoint — histological response, fibrosis improvement, or fat fraction?
phase 2 in liver disease is a different evidence question from weight
Yes — nothing containing this is approved anywhere, which is the first fact and usually the last one mentioned.
Biopsy-confirmed population or imaging-selected?
Which phase and which arm are you quoting?
fibrosis improvement without worsening steatohepatitis is the phrase to learn
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.
Small fix — dual agonist, GLP-1 and glucagon. No GIP arm in this molecule.
biopsy-confirmed is not the same as imaging-suggested
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.
do not import intuitions from the obesity programmes
How fast was the escalation in that protocol?
glucagon agonism and energy expenditure is the mechanistic thread
Has anyone posted an independent purity result for this compound?
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
glucagon agonism and energy expenditure is the mechanistic thread
This is the framing the board needs. It is a hepatic programme first.
This is the framing the board needs.
Disagreeing with this bit: that number comes from a different programme with a different population.
Disagreeing with this bit: that number comes from a different programme with a different population.
kaia_wojcik is right that biopsy and imaging endpoints are not interchangeable.
MASH endpoints are histological, which is a much harder bar
the titration in the trials was slow and deliberate
- 1How fast was the escalation in that protocol?9 comments in this branch · started by u/rania_marchand
- 2Yes — nothing containing this is approved anywhere, which is the first fact…7 comments in this branch · started by u/vitamin_d_void