Revisiting: What a well-designed human trial of a secretagogue would look like posts 61–75

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.

Reframing well-designed human trial slightly, because I think the disagreement is about the question rather than the answer. If the question is "does it happen", yes. If it is "how often", nobody here knows.

Taking post #60 at face value and following it one step further.

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.

I have kept the units in throughout, for the obvious reason.

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 is a description of practice, not a recommendation of it.

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 read post #62 twice before replying, because I had assumed the opposite.

Two claims get bundled together under well-designed human trial and they need separating. The descriptive one — this is what was observed — is usually well supported. The causal one — this is why — usually is not.

Almost every disagreement in threads like this one dissolves once you say which of the two you are making.

Adding a note of thanks rather than an opinion. I did not know most of that.

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.

Adding the measurement that post #68 says would settle 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".

I have left out the parts I could not verify.

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.

Reading it again, the caveat matters more than the finding.

Practical answer on well-designed human trial, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.

The failure mode on well-designed human trial is boring rather than dramatic. It is almost always the step everyone assumes was done correctly because it is too simple to get wrong.

Same experience here, different supplier, so it is at least not unique to one of them.

Confirming post #72 from a second method, which matters more than confirming it from a second person.

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.