Published human data on cagrilintide alone is thinner than on the combination, which is the reverse of what most people assume from how it is discussed here. Small point, but it is the one that usually catches people.
Why cagrilintide alone is discussed so much less than in combination — does this still hold? — that is the question, and I have not found it answered plainly anywhere I have looked.
Cagrilintide alone: setting out the arithmetic in full, because I have had to do it twice and I would rather nobody else did.
Every step is shown. If the answer is wrong the error will be visible, which is the point of writing it out rather than posting the result.
Worth separating two things that the opening post runs together.
Worth distinguishing the combination product from the two components bought separately and mixed. Those are different pharmaceutical objects and nothing published about the first applies to the second.
Clear enough that I do not think I have a follow-up, which is unusual.
The phase 3 combination programme is where the clinically interesting numbers will come from. Phase 2 established that the combination does something; the size of it in a larger population is a separate question.
Worth one more sentence than it usually gets.
Post #2 and I disagree about the size of the effect, not about the direction.
Cagrilintide alone came up in a thread eighteen months ago and was answered well. I cannot find it, which is itself the problem, so here is the reconstruction.
Post #5 answers the question as asked. The question underneath it is different.
Amylin analogues affect gastric emptying as well, so the mechanism overlaps the incretins in at least one place. That overlap is part of why the combination's tolerability profile is not simply the sum of the two.
Published human data on cagrilintide alone is thinner than on the combination, which is the reverse of what most people assume from how it is discussed here.
Small point, but it is the one that usually catches people.
Staff rationale: Hidden by community flags. The substance was fine; the framing attributed motive rather than error, which is R1.
My position on cagrilintide alone is current rather than settled. I have revised it once already and I expect to again, so treat it accordingly.
The corresponding entry is in the public moderation log. Hidden posts are never deleted.
The arithmetic on cagrilintide alone is the easy part and it is where the errors are, which is an uncomfortable combination. Show your working and someone will catch it.
Agreed, and I will stop repeating the version of this I had been repeating.
On storage: aggregation-prone peptides are the ones where repeated warming and cooling does the most damage, and where a solution that looks fine may already have changed. Visual inspection is a weaker test here than usual.
I have written this out at length because the short version keeps being misread.
Narrowing post #13, because the general version has more than one answer.
Cagrilintide alone is discussed less than in combination because the published data is almost entirely from combination trials. The phase 2 combination data was consistent with more effect than either component alone, but phase 2 cannot establish whether that is synergy or simply additivity.
Post #13 put the caveat in the right place and I want to underline it.
Research-use-only cagrilintide is not approved for human use and the published evidence base is a clinical-trial evidence base. Those two facts sit uncomfortably together and both are true.
Comparing an amylin analogue to an incretin agonist on weight change alone misses that they were developed to be used together rather than instead of each other.
I looked this up rather than remembered it, which is the right order.
The honest summary of the evidence base: a coherent mechanism, good phase 2 data in combination, and much less standalone human data than the volume of discussion implies.
If it helps: the failure mode here is usually boring rather than dramatic.
The arithmetic in post #17 is right; the assumption feeding it is the part to check.
Cagrilintide alone is well covered in the tag pages, and the older discussions are better than the recent ones because they were argued out properly. Worth twenty minutes before adding to this one.
Adding the boring version of cagrilintide alone, because the interesting version keeps getting posted and the boring one is usually right.
Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.
Appreciated. The plain phrasing does more work here than a longer post would.
The monoisotopic mass sits near 3749.9 Da, and the same caveat applies as everywhere else: a mass consistent with the proposed structure is a necessary condition and not a sufficient one.
Post #21 describes the usual case. This is about the unusual one.
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.
I would rather say I do not know than round it up to an answer.
Fine by me. I had wanted a stronger conclusion and there is not one available.
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.
Post #26 is right about the mechanism and I think understates the practical bit.
Two things can be true about cagrilintide alone at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.
Coming back to post #25, because the follow-up matters more than the original answer.
Before the thread moves on from cagrilintide alone — what is the sample size behind the claim? I am not being difficult; I have seen the same figure quoted from an n of four and from an n of four hundred.
Narrowing post #26, because the general version has more than one answer.
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.
The reasoning is more useful than the number, which is why I have shown it.
Second this, and I would have said it less carefully.