[Question] co-agonism — what am I missing here
Slightly embarrassed to be asking this, but: co-agonism — what am I missing here.
Complementary mechanisms are the rationale for pairing: satiety signalling alongside incretin signalling, rather than more agonism at the same receptor.
Nothing containing this compound is approved as a standalone product, and research-use-only material is not approved for human use.
Independent purity data on this compound is sparse compared with the older molecules, simply because far fewer members have paid for testing. Sparse data means wide uncertainty, not a verdict.
Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.
best — the order this archive was captured in
Independent result added to the log. Thank you for paying for it — there are very few on this compound.
Are you comparing against a GLP-1 monotherapy result? They are not comparable.
The engineering problem was duration: native amylin is short-acting and aggregation-prone. A long-acting analogue suitable for weekly administration is what makes the combination clinically interesting.
Monotherapy arm or combination arm?
long-acting amylin is the whole point of the molecule
read the combination arms separately from the monotherapy arms
nausea profile in the combination trials is the thing to read carefully
Sent a vial to VendorInvestigate because there was almost nothing on file for this compound. 98.5% against a claimed 98.0%, and I posted it because the log needs entries.
Correction: that is the combination programme, not the monotherapy readout. Different arms, different numbers.
do not assume the dosing intuitions from the GLP-1 boards transfer
independent purity data on this compound is thin
That result is preclinical. Worth flagging, since the thread has been reading it as human data.
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Small fix — amylin analogue, not a GLP-1 analogue. The whole mechanism argument changes on that word.
Right, and the tolerability data in the combination arms is the part worth reading properly rather than summarising.
How many separate lots has anyone here tested?
nothing here is approved as a standalone product and research material is not for human use
nothing here is approved as a standalone product and research material is not for human use
This is the distinction that keeps this board honest — different axis, not a stronger version of the same one.
REDEFINE is the combination programme
satiety signalling rather than incretin signalling
Push back: the evidence base here is thin enough that a confident ranking against the established compounds is not supportable.
Agreed — it is an amylin analogue and importing intuitions from the incretin boards produces confident nonsense.
What does the tolerability table in that paper actually say?
Careful — that is a dosing intuition carried over from another board and there is no basis for it here.
the co-agonism argument is about complementary mechanisms
Yes. The combination is where the interesting effect sizes are, and the monotherapy arms read very differently.
amylin analogue, different receptor family, different story
amylin and GLP-1 are not redundant pathways
amylin and GLP-1 are not redundant pathways
Disagreeing with this line: that figure is from a combination arm and is being quoted as monotherapy.
Agreed that the monotherapy numbers look modest out of context and that the context is the whole story.
- 1read the combination arms separately from the monotherapy arms15 comments in this branch · started by u/plain_titration