Second pass at: Cagrilintide's dosing interval and the pharmacokinetics behind it

On the subject in the title: Second pass at: Cagrilintide's dosing interval and the pharmacokinetics behind it Working notes rather than a conclusion.

Session topic: SURMOUNT-1 (N Engl J Med, 2022). Please read it before posting; the discussion is much better when everyone has.

The question I would like us to start with is what the trial set out to estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

post #2 answers the question as asked. The question underneath it is different.

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.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

I read post #4 twice before replying, because I had assumed the opposite.

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.

Cagrilintide molecular characteristics: it is a synthetic amylin analogue, substituted to prevent the amyloidogenicity of human amylin. The sequence is short and analytically straightforward to confirm by LC-MS.