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Compounds · Secretagogues & GH axis · continued

Why this subcategory is stricter about sourcing than most posts 31–53

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.

CD
cohort_driftTL3Regular18 May 2026#31

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

0 likes 2mo
SO
s.okonkwoTL2 Moderator20 May 2026#32

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.

21 likes 2mo
ID
isotonic_driftTL1Member22 May 2026#33
stopper_trace, post #25: 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. Go to post

Worth separating two things that post #29 runs together.

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.

9 likes in reply to #25 2mo
MN
m.ndiayeTL2 Moderator25 May 2026 · edited#34

post #33 is right about the mechanism and I think understates the practical bit.

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.

2 likes 2mo
CN
c.niemelTL3Regular27 May 2026#35

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

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.

0 likes 2mo
ND
n.dziedzicTL2 Moderator30 May 2026#36

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.

29 likes 2mo
B
BramleyTL2Member1 Jun 2026#37
m.guerrero, post #24: 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. Go to post

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.

14 likes in reply to #24 2mo
RC
r.chukwuTL2 Moderator3 Jun 2026#38

post #37 answers the question as asked. The question underneath it is different.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

5 likes 2mo
K
KStephanopoulosTL3Regular6 Jun 2026#39

CJC-1295 with and without DAC: the version with a drug affinity complex binds albumin covalently and persists for days. The version without it does not persist. Supplier labelling frequently does not distinguish them clearly, so confirming which you have is important.

0 likes 2mo
HC
h.castellanosTL2 Moderator8 Jun 2026#40

This follows post #37 rather than contradicting it.

Ipamorelin selectivity claims originate in preclinical characterisation and are reasonably well supported for what they claim: less effect on cortisol and prolactin than earlier GHRPs. Whether that translates to something clinically meaningful is a different question from whether the selectivity is real.

0 likes 2mo
JL
j.lokkenTL2 Moderator10 Jun 2026#41

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.

0 likes 2mo
SS
s.stavrianosTL2Member13 Jun 2026#42

Coming back to post #40, 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.

2 likes 1mo
LK
l.krastevTL2 Moderator15 Jun 2026#43
vial_slope, post #27: This follows post #24 rather than contradicting it. 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. Go to post

post #42 answers the question as asked. The question underneath it is different.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

14 likes in reply to #27 1mo
D
DKwiatkowskiTL3Regular17 Jun 2026#44

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.

28 likes 1mo
EK
ew.kuuselaTL2 Moderator19 Jun 2026#45

This follows post #42 rather than contradicting it.

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.

0 likes 1mo
TW
t.waldenstrmTL2Member22 Jun 2026#46

I read post #44 twice before replying, because I had assumed the opposite.

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.

0 likes 1mo
GD
g.danquahTL2 Moderator24 Jun 2026#47
c.niemel, post #35: Coming back to post #33, because the follow-up matters more than the original answer. 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. Go to post

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.

9 likes in reply to #35 1mo
B
BuchholzTL2Member26 Jun 2026#48
t.waldenstrm, post #46: I read post #44 twice before replying, because I had assumed the opposite. 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. Go to post

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

20 likes in reply to #46 1mo
EN
e.nilsenTL2 Moderator28 Jun 2026#49

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.

2 likes 30d
AL
aliquot_lineTL3Regular1 Jul 2026#50
n.hartmann, post #26: 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. Go to post

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.

8 likes in reply to #26 27d
LF
l.ferreiraTL2 Moderator3 Jul 2026#51

On post #47 — agreed on the reasoning, with one qualification.

Ipamorelin selectivity claims originate in preclinical characterisation and are reasonably well supported for what they claim: less effect on cortisol and prolactin than earlier GHRPs. Whether that translates to something clinically meaningful is a different question from whether the selectivity is real.

12 likes 25d
HK
h.koodziejTL2Member5 Jul 2026 · edited#52
integrator_draft, post #12: 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. Go to post

CJC-1295 with and without DAC: the version with a drug affinity complex binds albumin covalently and persists for days. The version without it does not persist. Supplier labelling frequently does not distinguish them clearly, so confirming which you have is important.

4 likes in reply to #12 23d
AA
an.adeyemiTL2 Moderator7 Jul 2026#53
g.danquah, post #47: 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. Go to post

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.

0 likes in reply to #47 21d

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