Secretagogues and glucose tolerance: the mechanistic concern — what changed since

Secretagogues and glucose tolerance: the mechanistic concern — what changed since Writing it up because I had to work it out twice and would rather nobody else did.

I have seen STEP 1 (N Engl J Med, 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 opening post answers the question as asked. The question underneath it is different.

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.

Reading a rodent study on a secretagogue without over-extrapolating: rodent studies can show a mechanism is plausible. They cannot show magnitude of effect in humans or safety profile in humans. That gap is larger for secretagogues than for incretin agonists because the human evidence is thinner.

Worth separating two things that the opening post runs together.

Why this subcategory is stricter about sourcing than most: the evidence base is weaker and that is precisely why documentation quality matters more. A supplier page that clearly identifies the compound and the purity is more valuable for secretagogues than for incretin agonists where the evidence base is stronger.

Evidence quality in the secretagogue literature is honestly weaker than in the incretin literature. Large randomised controlled trials are rare. Most evidence is mechanistic or from small studies. This is why this subcategory has higher sourcing standards than most.