On the subject in the title: Revisiting: What a well-designed human trial of a secretagogue would look like Working notes rather than a conclusion.
Something about well-designed human trial does not reconcile and I would like a second pair of eyes before I decide which half is wrong.
Two sources, both reputable, giving figures that cannot both be right unless they are measuring different quantities. My suspicion is that they are, and I cannot see how.
The opening post put the caveat in the right place and I want to underline it.
Well-designed human trial is well covered in the tag pages, and the older discussions are better than the recent ones because they were argued out properly. Worth twenty minutes before adding to this one.
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.
That is one dataset and I would not build a rule on it.
Answering the well-designed human trial question as asked, then the question I think is meant. As asked: yes, with the qualification below. As meant: it depends on how the first measurement was taken.
Post #4 and I disagree about the size of the effect, not about the direction.
Nobody has said the unglamorous part of well-designed human trial yet, so: most of the variation is explained by things that are boring to write about and easy to check.
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.
Two people in this thread mean different things by well-designed human trial and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.
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".
That holds for the case as described. Change the assumptions and it may not.
One caution on well-designed human trial: everything above assumes the underlying documentation is what it claims to be. That assumption is doing real work and is rarely stated.
Worth separating two things that post #11 runs together.
The version of well-designed human trial that I was taught turned out to be a teaching simplification. Useful, and not true in the way I had assumed it was.
This follows post #11 rather than contradicting it.
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.
On well-designed human trial, I would rather understate and be corrected upward than overstate and be quoted. That is a house style here and it is a good one.
That is a fair summary of where the discussion has got to.
On post #15 — agreed on the reasoning, with one qualification.
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.
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.
Confirming post #19 from a second method, which matters more than confirming it from a second person.
What I would check first on well-designed human trial is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
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 read post #18 twice before replying, because I had assumed the opposite.
Taking well-designed human trial seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.
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.
The literature is thinner on this than the confidence in the thread implies.
I had read the opposite somewhere and cannot now find where, which tells me something.
Agreed on well-designed human trial, with one qualification that I think matters. The reasoning holds for the case as described. Change the starting assumption and it does not, and the starting assumption is the part nobody states.
A methods point on well-designed human trial rather than a substantive one: if the comparison is not like for like, the difference you are measuring is the difference in method.
Taking post #25 at face value and following it one step further.
On analysis: these are short peptides and generally straightforward chromatographically, which means a poor purity result is more likely to reflect the synthesis than the method.
Flagging that the sources on this are thinner than the confidence in the thread suggests.
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.
Genuinely open to being wrong about this one.
The arithmetic in post #28 is right; the assumption feeding it is the part to check.
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.
One of those cases where knowing the mechanism does not help the decision.