Reading a rodent study on a secretagogue without over-extrapolating

Posting this under the heading it deserves: Reading a rodent study on a secretagogue without over-extrapolating Everything below is what sits behind that.

I have seen STEP 8 (JAMA, 2022) 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.

What a well-designed human trial of a secretagogue would look like: randomised, placebo-controlled, adequate sample size, IGF-1 as primary outcome, muscle and strength as secondary outcomes, adequate follow-up duration. Very few secretagogue trials meet that description.

CJC-1295 with and without DAC: the version with a drug affinity complex binds albumin covalently and persists for days. The version without it does not persist. Supplier labelling frequently does not distinguish them clearly, so confirming which you have is important.

Coming back to post #20, because the follow-up matters more than the original answer.

Secretagogues and glucose tolerance: there is a mechanistic concern that sustained growth hormone elevation might impair glucose tolerance. The clinical relevance of this concern in practice is not well established.

Development history is more informative than speculation: ipamorelin was investigated clinically for post-operative ileus and was not taken forward to registration. That it was not brought to market tells you something about the cost-benefit calculation that any amount of forum enthusiasm does not.

This follows post #35 rather than contradicting it.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

This follows post #44 rather than contradicting it.

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.

CJC-1295 with and without DAC: the version with a drug affinity complex binds albumin covalently and persists for days. The version without it does not persist. Supplier labelling frequently does not distinguish them clearly, so confirming which you have is important.