This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
That reframing is the whole thing. The facts I already had.
Adding a null result on well-designed human trial. I looked, carefully, and found nothing, and null results deserve posting precisely because they never are.
Where I part company with post #29, and it is a narrow parting.
Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.
Speaking for myself and not for anyone else who has posted here.
Post #33 is the version of this I will quote in future. One addition.
Tesamorelin has an approved indication in HIV-associated lipodystrophy. That is the only compound in this class with a registration-quality evidence base from a proper trial programme. Generalising from that narrow population to healthy adults is a substantial extrapolation.
Not the whole picture, but the part of it I can speak to.
Everything in post #33 holds. The case it does not cover is the one I have.
The strongest argument against my own position on well-designed human trial, stated as well as I can state it, since nobody else has yet.
Distinguishing three things in the well-designed human trial discussion that keep getting used interchangeably: the observation, the proposed mechanism, and the recommendation that gets attached to both.
Building on post #37 rather than restating 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.
Adding the caveat now so it does not have to be extracted later.
On post #37 — agreed on the reasoning, with one qualification.
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.
One case, stated as one case.
Picking up post #37: that is the part I would want checked first.
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.
I keep a log of this specifically because memory is unreliable about it.
Adding the measurement that post #38 says would settle it.
Well-designed human trial: I would want to see the raw numbers rather than the summary before agreeing. Summaries lose exactly the information that would settle this.
Post #40 describes the usual case. This is about the unusual one.
The reason well-designed human trial is hard to answer is that the obvious measurement and the relevant quantity are not the same thing, and substituting one for the other is silent.
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.
I would be interested in a counterexample if anyone has one.
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.
I came in to disagree and I am leaving without a disagreement.
Hexarelin and the earlier peptidyl secretagogues have more published human data than the newer ones and a less favourable profile, which is worth knowing before treating "newer" as "better characterised".
Worth reading the earlier posts in this thread before acting on mine.
Well-designed human trial was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.
A mass result for a short peptide is more discriminating than for a long one, because a single residue difference is a larger proportion of the total. That makes identity confirmation genuinely useful here.
A single observation, in a thread that deserves better than single observations.
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.
Picking up post #51: that is the part I would want checked first.
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.
I have no financial interest in anything named in this thread and I want to say so before I comment on well-designed human trial, because it is the sort of subject where it matters.
This follows post #55 rather than contradicting it.
Injection-site reactions are reported more often in this family than for the incretins. Whether that is the compounds or the preparations they are typically supplied in is not established.
A guess, clearly labelled as one.
Coming back to post #55, because the follow-up matters more than the original answer.
GHRH analogues versus ghrelin mimetics are often conflated but they are different mechanisms. GHRH analogues (like CJC-1295) cause the pituitary to release growth hormone. Ghrelin mimetics (like GHRPs) act on the ghrelin receptor directly. The effect on growth hormone secretion is similar but the mechanisms are distinct.
Adding a reference point for well-designed human trial. Mine is a single case, collected without controls, and I am posting the method alongside it so it can be discounted appropriately.
Tesamorelin has an approved indication in HIV-associated lipodystrophy. That is the only compound in this class with a registration-quality evidence base from a proper trial programme. Generalising from that narrow population to healthy adults is a substantial extrapolation.
Effects reported at the level of appetite are the most consistently described and the most mechanistically direct for the ghrelin-receptor compounds, which is not what most people are taking them for.
The short version is the first sentence; the rest is why.