[Trial Data] nausea rates in the combination arm vs sema alone
nausea rates in the combination arm vs sema alone — a position I have arrived at slowly and would like tested.
Went looking for independent results on this and found a handful across the whole site. That is the honest state of the evidence.
Asked a question here that turned out to be based on a mechanism confusion. Three people untangled it patiently.
Kept a log purely because so few people are logging this one. It is one person and it is not data.
Would rather be corrected in public than confident in private.
best — the order this archive was captured in
Why this compound is not simply another agonist, which is how it gets described everywhere else.
Amylin is co-secreted with insulin and signals satiety through its own receptor complexes. It is a different axis from the incretin system, not a parallel version of it. That is why the combination story is interesting: two mechanisms that address appetite differently, rather than more agonism at one receptor.
It is also why the dosing intuitions people bring from the semaglutide and tirzepatide boards do not transfer. Different receptors, different exposure-response, and no published schedule anybody here can reason from.
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.
Agreed — it is an amylin analogue and importing intuitions from the incretin boards produces confident nonsense.
the interesting data is the combination, not the monotherapy
Sent a vial to PeptideMeter because there was almost nothing on file for this compound. 99.6% against a claimed 99.0%, and I posted it because the log needs entries.
Carried an assumption over from the tirzepatide board and was corrected within an hour. Deserved.
Disagree — you are quoting a combination arm as though it were monotherapy. Those are different results.
satiety signalling rather than incretin signalling
Bought small deliberately because the evidence base is thin. That felt like the only defensible approach.
That result is preclinical. Worth flagging, since the thread has been reading it as human data.
long-acting amylin is the whole point of the molecule
That result is preclinical.
Disagreeing with this line: that figure is from a combination arm and is being quoted as monotherapy.
REDEFINE is the combination programme
amylin analogue, different receptor family, different story
- 1Bought small deliberately because the evidence base is thin. That felt like…6 comments in this branch · started by u/forest_plot_fiona