On the subject in the title: Evidence quality in the secretagogue literature: an honest assessment Working notes rather than a conclusion.
A follow-up question about Evidence quality that I did not know to ask the first time.
The earlier thread answered what I asked. What I should have asked is below, and I think it is the one that matters.
Building on post #2 rather than restating it.
The useful distinction on Evidence quality is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars.
The opening post put the caveat in the right place and I want to underline it.
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.
That has been true for the cases I have seen and I have not seen many.
Post #2 answers the question as asked. The question underneath it is different.
The most useful thing anyone has posted about Evidence quality in this category was a table of what had been measured and by whom. That is what I would want again.
Tesamorelin is the compound in this family with the strongest regulatory evidence base, and it was studied in a specific population for a specific indication. That evidence does not generalise to the way it is usually discussed.
Post #7 is right about the mechanism and I think understates the practical bit.
Reconstitution volumes in this family are often small enough that dead volume in the syringe is a meaningful fraction of the dose. A fixed-needle insulin syringe is worth the trouble here specifically.
Coming back to post #9, because the follow-up matters more than the original answer.
Research-use-only secretagogues are not approved for human use. That statement is doing real work in this subcategory, where the published evidence base is thinner than the volume of confident discussion.
It is one reading of the data and not the only reasonable one.
Answering the question post #7 raises rather than the one it answers.
The most useful single question to ask about any compound in this family is what the published human evidence actually consists of. In several cases the honest answer is a handful of small studies.
For anyone finding this later: the short answer on Evidence quality is that it depends on one thing, and the rest of the thread is people identifying which thing.
Evidence quality is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for.
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.
If that reads as pedantic, it is, and it has saved me twice.
I disagree with the framing of Evidence quality above, and I think it is a substantive disagreement rather than a terminological one. Setting out why, so it can be checked.
The reasoning depends on an assumption that is doing a lot of work and is never stated. If the assumption holds, the conclusion follows. I do not think it holds generally.
Source for the Evidence quality figure, since it was asked for. It is in the discussion rather than the abstract, which is why the version circulating is stronger than the paper is.
Reading the surrounding paragraph is worth the two minutes. The authors are more careful than their summarisers.
Taking post #15 at face value and following it one step further.
Growth hormone secretagogues act on the ghrelin receptor or on the growth hormone releasing hormone receptor rather than supplying growth hormone, which is the distinction that matters for anyone reading the literature.
I would put moderate confidence on the mainstream reading of Evidence quality and no more. That is not scepticism for its own sake; it is where the sourcing actually stops.
Picking up post #19: that is the part I would want checked first.
The question underneath Evidence quality is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.
Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.
Storage: these are lyophilised short peptides and are generally reasonably stable dry and considerably less so in solution. Reconstituting only what will be used within the period the supplier's own data covers is the conservative approach.
Not a conclusion. A place to stand while looking for one.
The arithmetic in post #20 is right; the assumption feeding it is the part to check.
The pulsatile character of endogenous growth hormone release is why a secretagogue and exogenous growth hormone are not interchangeable, and why a single measured level tells you very little about either.
Answering the question post #23 raises rather than the one it answers.
Published human data on most of this family is thin, old, or from small studies with surrogate endpoints. That is a genuine limitation and it is the honest answer to most questions in this subcategory.
Confirming post #24 from a second method, which matters more than confirming it from a second person.
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.
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