[Caution] CagriSema trial ratios are fixed-dose, do not extrapolate to self-mixing
CagriSema trial ratios are fixed-dose, do not extrapolate to self-mixing — a position I have arrived at slowly and would like tested.
Reading the trial literature on this without misleading yourself.
Separate the monotherapy arms from the combination arms before you do anything else. They report different effect sizes and different tolerability, and almost every summary that circulates blends them.
Then read the tolerability tables rather than the headline. In combination work the interesting question is whether adding a second mechanism adds effect without adding proportionate side effects, and that question is answered in a table nobody quotes.
Finally, note the durations. Comparing a shorter readout here with a longer one from an established compound is not a comparison at all.
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.
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
Complementary mechanisms are the rationale for pairing: satiety signalling alongside incretin signalling, rather than more agonism at the same receptor.
Asked a question here that turned out to be based on a mechanism confusion. Three people untangled it patiently.
phase 3 data will change most of what gets said here
That result is preclinical. Worth flagging, since the thread has been reading it as human data.
Small fix — amylin analogue, not a GLP-1 analogue. The whole mechanism argument changes on that word.
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.
the monotherapy numbers are modest and that is not the point
the monotherapy numbers are modest and that is not the point
lane_map_larry is right that the evidence base here is thin. Conclusions should be held loosely.
Yes. The combination is where the interesting effect sizes are, and the monotherapy arms read very differently.
Went looking for independent results on this and found a handful across the whole site. That is the honest state of the evidence.
Went looking for independent results on this and found a handful across the whole site.
Disagreeing with this line: that figure is from a combination arm and is being quoted as monotherapy.
amylin analogue, different receptor family, different story
- 1Complementary mechanisms are the rationale for pairing: satiety signalling…7 comments in this branch · started by u/tomas_kimani
- 2the monotherapy numbers are modest and that is not the point7 comments in this branch · started by u/lane_map_larry