reading REDEFINE threads from 2024 and half of it aged badly
reading REDEFINE threads from 2024 and half of it aged badly. Making the case below, and I expect to lose some of it in the comments.
Complementary mechanisms are the rationale for pairing: satiety signalling alongside incretin signalling, rather than more agonism at the same receptor.
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 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.
Would rather be corrected in public than confident in private.
best — the order this archive was captured in
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.
Same view — long-acting is the engineering achievement here, and it is why the molecule exists at all.
Carried an assumption over from the tirzepatide board and was corrected within an hour. Deserved.
Combination and monotherapy arms must be read separately. Efficacy and tolerability both differ substantially between them and summaries routinely blur the two.
Same view — long-acting is the engineering achievement here, and it is why the molecule exists at all.
Disagreeing with this line: that figure is from a combination arm and is being quoted as monotherapy.
Disagreeing with this line: that figure is from a combination arm and is being quoted as monotherapy.
This is the distinction that keeps this board honest — different axis, not a stronger version of the same one.
I would not extrapolate the tolerability profile from the monotherapy arm to the combination. The trials report them separately for a reason.
do not assume the dosing intuitions from the GLP-1 boards transfer
Cosigning on the thin independent data. Fewer members test this, so the bands are wider and should be treated that way.
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Monotherapy arm or combination arm?
Asked a question here that turned out to be based on a mechanism confusion. Three people untangled it patiently.
Sent a vial to Medutest because there was almost nothing on file for this compound. 97.6% against a claimed 97.0%, and I posted it because the log needs entries.
independent purity data on this compound is thin
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.
This. Complementary mechanisms rather than more of the same is the actual argument for the pairing.
Small fix — amylin analogue, not a GLP-1 analogue. The whole mechanism argument changes on that word.
Kept a log purely because so few people are logging this one. It is one person and it is not data.
Kept a log purely because so few people are logging this one.
ines_ekstrom is right that the evidence base here is thin. Conclusions should be held loosely.
Kept a log purely because so few people are logging this one.
Adding the standing caveat — nothing here is approved standalone and research material is not for human use.
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.
amylin analogue, different receptor family, different story
Yes. The combination is where the interesting effect sizes are, and the monotherapy arms read very differently.
Independent result added to the log. Thank you for paying for it — there are very few on this compound.
Independent result added to the log.
Agreed, and the combination arms are where the interesting numbers actually live.
Push back: the evidence base here is thin enough that a confident ranking against the established compounds is not supportable.
That result is preclinical. Worth flagging, since the thread has been reading it as human data.
the co-agonism argument is about complementary mechanisms
- 1Cosigning on the thin independent data. Fewer members test this, so the…10 comments in this branch · started by u/rina_sobczak
- 2Same view — long-acting is the engineering achievement here, and it is why…7 comments in this branch · started by u/yara_mensah