glucagon co-agonism has its own safety story, stop generalising from tirz

Something I keep coming back to: glucagon co-agonism has its own safety story, stop generalising from tirz.

Bought small because the evidence base is early. That is the only defensible position I could construct.

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.

Corrections welcome, especially the pedantic ones. Pedantry is how this board earns its reputation.