Revisiting: What a well-designed human trial of a secretagogue would look like

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.

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.

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.

Coming back to post #33, because the follow-up matters more than the original answer.

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.

Picking up post #38: that is the part I would want checked first.

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.

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.

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.

IGF-1 as a surrogate: it is a better integrated measure than a spot growth hormone level and it is still a surrogate, with all the caveats that come with surrogates. Stable or rising IGF-1 is not the same as "this is working" in any health-related sense.

post #68 is right about the mechanism and I think understates the practical bit.

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.