how much of what we believe about amylin actually comes from co-agonism threads
Question in the title, detail here: how much of what we believe about amylin actually comes from co-agonism threads.
Dosing intuitions from the GLP-1 boards do not transfer. Different receptor family, different exposure-response, and no published schedule for members to reason from.
Carried an assumption over from the tirzepatide board and was corrected within an hour. Deserved.
Read the combination paper twice before saying anything here. The monotherapy and combination arms tell genuinely different stories.
Screenshot none of this. Read the whole thread, including the parts where I am told I am wrong.
best — the order this archive was captured in
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.
amylin and GLP-1 are not redundant pathways
Right, and the tolerability data in the combination arms is the part worth reading properly rather than summarising.
Not convinced. Amylin signalling is not a GLP-1 pathway and the mechanism you are proposing conflates them.
Agreed that the monotherapy numbers look modest out of context and that the context is the whole story.
Amylin is co-secreted with insulin and acts on satiety and gastric emptying through its own receptor complexes. An amylin analogue is therefore not a variant of an incretin agonist — it is a different signalling axis.
nothing containing this is approved as a standalone product
do not assume the dosing intuitions from the GLP-1 boards transfer
Careful — that is a dosing intuition carried over from another board and there is no basis for it here.
What does the tolerability table in that paper actually say?
Bought small deliberately because the evidence base is thin. That felt like the only defensible approach.
I would not extrapolate the tolerability profile from the monotherapy arm to the combination. The trials report them separately for a reason.
Sent a vial to Janoshik because there was almost nothing on file for this compound. 97.7% against a claimed 97.5%, and I posted it because the log needs entries.
Yes. The combination is where the interesting effect sizes are, and the monotherapy arms read very differently.
long-acting amylin is the whole point of the molecule
Push back: the evidence base here is thin enough that a confident ranking against the established compounds is not supportable.
Correction: that is the combination programme, not the monotherapy readout. Different arms, different numbers.
Yes. Anyone reading this board should hold their conclusions loosely until phase 3 reports.
Disagree — you are quoting a combination arm as though it were monotherapy. Those are different results.
Do you have the publication or a summary of it?
That is preclinical work and the thread is treating it as a human finding.
This. Complementary mechanisms rather than more of the same is the actual argument for the pairing.
Cosigning on the thin independent data. Fewer members test this, so the bands are wider and should be treated that way.
- 1Bought small deliberately because the evidence base is thin. That felt like…8 comments in this branch · started by u/nl_verzekering
- 2The engineering problem was duration: native amylin is short-acting and…6 comments in this branch · started by u/lukas_vermeulen