[Question] glucagon — what am I missing here
The title is the whole question — glucagon — what am I missing here — but here is why I am asking.
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.
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.
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.
Ask me anything specific. Anything general I will probably get wrong.
best — the order this archive was captured in
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.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.
Disagreeing with this bit: that number comes from a different programme with a different population.
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Agreed that the endpoint definitions matter enormously and almost nobody reads them before quoting a response rate.
phase 2 in liver disease is a different evidence question from weight
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
dual GLP-1 and glucagon agonist, and the glucagon arm is the story
Agreed — and the endpoint definitions are where the actual claim lives.
Imaging-derived liver fat fraction is a surrogate. It correlates with histology imperfectly, and a trial reporting one is not reporting the other.
Retitled to name the endpoint. Histological and imaging results are not interchangeable and the original title implied they were.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use.
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.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Correction: that is the imaging endpoint, not the histological one. The paper reports both and they differ substantially.
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