Second pass at: Why semaglutide's albumin binding is the whole reason weekly dosing works

Second pass at: Why semaglutide's albumin binding is the whole reason weekly dosing works Writing it up because I had to work it out twice and would rather nobody else did.

I have seen SURPASS-4 (Lancet, 2021) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

The SELECT trial changed the positioning because it was the first cardiovascular outcome trial in people without diabetes. That decoupled the cardiovascular argument from glycaemic control, which is why it mattered beyond its own numbers.

Coming back to the opening post, because the follow-up matters more than the original answer.

On alcohol: the labelling does not contraindicate it, but it raises gastric irritation risk and semaglutide already does that. There is no published interaction study and the conservative position is to limit it if you are titrating or if gastrointestinal symptoms are troublesome.