MASH — my 24-week log, condensed into one table
MASH — my 24-week log, condensed into one table, which sounds obvious until you try to state the evidence for it.
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.
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.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
If somebody has the same thing measured a different way, post it next to mine and we will see whether they agree.
best — the order this archive was captured in
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Removed the escalation schedule. Unapproved compound, no protocols for other members, no exceptions.
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
do not import intuitions from the obesity programmes
What does the tolerability table say at that dose?
Are you reading the publication or a summary?
How fast was the escalation in that protocol?
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.
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
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.
Same. Very thin independent data on this one, which should make everybody here more tentative than they are.
Same.
slow_logbook_notes30 is right that biopsy and imaging endpoints are not interchangeable.
That is an escalation schedule for an unapproved compound and this board does not host those.
That figure is from the obesity programme, and this thread is about the hepatic one.
MASH endpoints are histological, which is a much harder bar
the weight numbers are secondary to what this is being developed for
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.
- 1Independent purity results for this compound are very sparse across the…7 comments in this branch · started by u/clara_restrepo
- 2Same. Very thin independent data on this one, which should make everybody…6 comments in this branch · started by u/slow_logbook_notes30