Amylin signalling is distinct from GLP-1 signalling. Amylin slows gastric emptying and promotes satiety through a different receptor and different neural pathways. The hypothesis behind combination is two complementary satiety mechanisms with one injection.
Topic summary
Amylin analogue mechanism: satiety signalling separate from GLP-1
This is a generated summary. It shows the 9 most-liked posts from a topic of 143, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.
On post #28 — agreed on the reasoning, with one qualification.
Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.
The correction was fair and I had been repeating something I had not checked carefully enough.
30 likes 20mo
r.erdogan, post #19: This follows post #16 rather than contradicting it. I disagree with the reply above, and I think the disagreement is substantive rather than terminological. The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am… Go to post
Picking up post #48: that is the part I would want checked first.
The CagriSema phase 2 paper: a fixed combination of the two components in one weekly injection. The trade-off of a fixed combination is that you cannot titrate the components independently and you cannot attribute effect to one component from a combination trial.
For anyone arriving from searches on "amylin agonist": this subcategory discusses published clinical evidence and what it does and does not establish. It does not endorse or recommend the compounds discussed.
30 likes 17mo
ni.kravchenko, post #59: Nausea profile of amylin analogues: the historical agent pramlintide required multiple daily doses and had a difficult tolerability profile. A weekly formulation is a substantially different proposition and data from that is more relevant than data from pramlintide. Go to post
Worth separating two things that post #68 runs together.
The CagriSema phase 2 paper: a fixed combination of the two components in one weekly injection. The trade-off of a fixed combination is that you cannot titrate the components independently and you cannot attribute effect to one component from a combination trial.
m.ekstrom, post #31: Is synergy the right word for the combination data? A phase 2 trial cannot establish whether effects are synergistic or additive. Synergy is a mechanistic claim that requires a designed experiment to support it. The combination works, but the mechanism is unsettled. Go to post
For anyone arriving from searches on "amylin agonist": this subcategory discusses published clinical evidence and what it does and does not establish. It does not endorse or recommend the compounds discussed.
coldchain_liu, post #54: Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive. Go to post
The dosing interval: cagrilintide's half-life is roughly 7 to 8 days, suitable for weekly dosing. The pharmacokinetics are the reason the dosing schedule makes sense.
bench_notes, post #18: On post #14 — agreed on the reasoning, with one qualification. The dosing interval: cagrilintide's half-life is roughly 7 to 8 days, suitable for weekly dosing. The pharmacokinetics are the reason the dosing schedule makes sense. Go to post
post #128 answers the question as asked. The question underneath it is different.
What is genuinely unknown about long-term amylin agonism: real-world response rates, whether effect is durable with continued use, whether satiety adaptation occurs over months or years, safety profile in populations not enrolled in the trials.
Rodrigues, post #60: Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive. Go to post
post #133 is right about the mechanism and I think understates the practical bit.
Historical amylin analogues: pramlintide was the only long-acting amylin analogue licensed for some time and its poor adherence was a known limitation. A weekly formulation addresses that practical barrier.
Read the full topic (143 posts)
This topic was referenced in
- Follow-up: What is genuinely unknown about long-term amylin agonismCompounds › Cagrilintide & amylin analogues · 2 replies
- Second pass at: Reading a combination trial: attributing effect to componentsCompounds › Cagrilintide & amylin analogues · 43 replies
Moved from Retatrutide by t.vasquez. Category placement is not obvious from outside and getting it wrong is expected. This topic will get better answers here. The move is recorded in the public log citing R7.
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