three years of survodutide threads, summarised so you do not have to read them
three years of survodutide threads, summarised so you do not have to read them. Not a hot take, just something I have not seen said plainly here.
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 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.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
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.
Careful with the mechanism claim. Glucagon agonism is plausible as an explanation and it has not been isolated as the operative one.
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Which phase and which arm are you quoting?
Push back: the evidence here is phase 2, in a specific population, and it does not support a general ranking.
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MASH endpoints are histological, which is a much harder bar
MASH endpoints are histological, which is a much harder bar
Disagreeing with this bit: that number comes from a different programme with a different population.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
That figure is from the obesity programme, and this thread is about the hepatic one.
fibrosis improvement without worsening steatohepatitis is the phrase to learn
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.
a liver endpoint is not a weight endpoint with better marketing
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
biopsy-confirmed is not the same as imaging-suggested
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.
Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
the weight numbers are secondary to what this is being developed for
the weight numbers are secondary to what this is being developed for
Adding the standing caveat — unapproved compound, research material is not for human use.
Are you reading the publication or a summary?
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
patient_labslip_log is right that biopsy and imaging endpoints are not interchangeable.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
Same. Very thin independent data on this one, which should make everybody here more tentative than they are.
- 1Push back: the evidence here is phase 2, in a specific population, and it…11 comments in this branch · started by u/britt_abubakar