MuscleLedger

Growth Hormone Secretagogues: The Class, and What Its Trials Actually Measured

Every compound in this category reliably raises growth hormone. Almost none of them has ever been tested against a muscle endpoint, and the one that reached an approval reached it for fat.

Leon H · Published 2026-09-08

The compounds in this category are sold under a promise that is half true and rarely separated into its halves. They do raise growth hormone. That has been measured, in humans, repeatedly, and it is not seriously disputed by anyone. What has almost never been measured is the second half — whether the raised hormone turns into muscle you can use.

This page is the category page for that distinction. It is research journalism and contains no usage guidance; this site publishes no dose figures, and dosing questions are answered by Peptifact rather than here.

Two families under one label

A secretagogue is anything that makes a gland secrete. In this market the word covers two mechanically different things.

GHRH analogues copy growth hormone releasing hormone, the signal the hypothalamus sends to the pituitary. Sermorelin is a fragment of the natural hormone. Tesamorelin is a stabilised version of it. CJC-1295 is a long-acting version built to survive in the bloodstream for days rather than minutes.

Ghrelin-receptor agonists copy ghrelin, the stomach's hunger signal, which acts on an entirely different receptor and also triggers GH release. Ipamorelin, hexarelin, GHRP-2 and GHRP-6 are peptides that do this. MK-677 does it too, and is not a peptide at all.

The practical consequence of the split is that the two families stack — vendors sell a GHRH analogue and a ghrelin-receptor agonist together because they push two different buttons on the same machine. The evidential consequence is that they have to be assessed separately, and this page does.

The registry footprint of the whole class

Searched 2026-09-08.

Compound Family PubMed records Indexed RCTs US approval
Tesamorelin GHRH analogue 121 26 Yes — EGRIFTA, BLA 022505, 2010-11-10
Sermorelin GHRH analogue 332 19 Formerly approved as GEREF; withdrawn from marketing
CJC-1295 GHRH analogue 33 0 indexed No
Ipamorelin Ghrelin agonist 54 2 No
Hexarelin Ghrelin agonist 313 — No
GHRP-6 Ghrelin agonist 785 — No
MK-677 Ghrelin agonist (non-peptide) 138 18 No

Two things fall out of that table immediately. The compound with by far the most human trial evidence is the one that is not a peptide. And the only compound in the class with a live US approval got it for something other than muscle.

One compound frequently sold on the same shelf does not belong in this table at all. SS-31, or elamipretide, does not act on the growth hormone axis in any way — it binds cardiolipin in the mitochondrial membrane — and it holds a 2025 US approval of its own. Vendors group it here; pharmacology does not.

The one approval, and what it is for

Tesamorelin was approved on 10 November 2010 under BLA 022505 as EGRIFTA, sponsored by Theratechnologies. It is a GHRH analogue, mechanically the same family as CJC-1295 and sermorelin, and it works — the approval rests on trials showing it reduces excess visceral abdominal fat in people with HIV-associated lipodystrophy.

That indication is worth reading slowly. A regulator looked at the best-developed GHRH analogue in existence, reviewed its trial programme, and approved it to move fat around in a specific clinical population. Not to build muscle. Not to improve strength. Not for athletes, and not for healthy adults of any description.

This is the strongest available evidence about what raising GH does in practice, because it is the only claim in this class that has ever survived a regulatory review. It is a fat claim.

The endpoint problem

Read the trials in this category in sequence and a pattern appears that is more informative than any individual result: the trials that measured hormones succeeded, and the trials that measured function mostly did not.

The clearest case is CJC-1295. Its single human study, published in The Journal of Clinical Endocrinology & Metabolism in 2006, ran two randomised, placebo-controlled ascending-dose trials over 28 and 49 days in healthy adults aged 21 to 61, and reported dose-dependent increases in mean plasma GH of two- to ten-fold lasting six days or more, IGF-1 up 1.5- to three-fold for nine to eleven days, and an estimated half-life between 5.8 and 8.1 days. It is a competent, informative pharmacology study. Its outcome measures were peak concentrations and areas under the curve. There was no body-composition endpoint, no strength endpoint and no function endpoint, and in the twenty years since, none has been added. The full account is here.

Ipamorelin is the same story with a different shape. It has three registrations on ClinicalTrials.gov and not one concerns muscle; its largest completed trials were run by a pharmaceutical sponsor for recovery of gastrointestinal function after bowel surgery, and the one with published results missed its key efficacy endpoint.

The two exceptions are the two compounds in the class that were developed as oral drugs for age-related muscle loss, and both were tested properly:

  • MK-677, over 12 months in 65 adults aged 60 to 81, raised fat-free mass by 1.1 kg against a 0.5 kg fall on placebo — and its authors reported that the increased fat-free mass "did not result in changes in strength or function", noting that the trial was not powered to evaluate those endpoints.
  • Capromorelin, in 395 adults aged 65 to 84, produced 1.4 kg of lean body mass against 0.3 kg on placebo, with a 0.9-second improvement in tandem walk — in a trial terminated early. Both results are set out on the MK-677 page.

So the honest summary of the class is: the hormone response is real and large, the body-composition response is real and small, and the functional response has been demonstrated once, modestly, in adults who already had a functional deficit.

Why fat-free mass overstates the case

Fat-free mass is not muscle. It is everything that is not fat, water included, and growth hormone is a fluid-retaining hormone — mild lower-leg swelling recurs as an adverse event across these trials because the mechanism does that. When a secretagogue trial reports a fat-free-mass gain, some fraction of it is water, and the trials that tried to separate the two by tracking intracellular water found the cell-mass change smaller than the headline.

This is not a technicality invented to be unkind to the category. It is the reason a compound can produce a genuine, statistically strong body-composition result and no strength result in the same participants, which is exactly what the largest muscle trial in this class reported.

Status: banned, and in FDA's category 2

For anyone in a tested pool, the whole category is prohibited at all times, in competition and out, under section S2.2 of the WADA Prohibited List, which names growth hormone releasing factors and their analogues alongside the GH secretagogues. The detection literature is substantial and, tellingly, larger than the efficacy literature for several of these compounds. Our drug testing page carries the per-compound detail and the published detection windows.

Separately, FDA's bulk drug substances lists place several members of this class in category 2 — substances that raise significant safety risks and may not be used in compounding — which is the status that separates a compound sold by a compounding pharmacy from one sold as "research chemical" only.

What this class is good for, stated plainly

If the goal is a higher IGF-1 number on a blood panel, these compounds do that, reliably, and the pharmacology is well described. If the goal is more muscle on a trained adult, the evidence does not exist — not because it came back negative, but because with two exceptions in older populations, nobody has run the trial. The compounds that did get properly tested produced about a kilogram of fat-free mass and no strength change.

Set that against the evidence ledger for the whole market, or against what a controlled trial of an anabolic steroid produced in trained men, which is the comparison our page on peptides versus steroids works through. The gap is not subtle, and pretending otherwise is how this category gets sold.

Sources

  • Teichman SL et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 2006. PMID 16352683
  • Nass R et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults. Ann Intern Med 2008. PMID 18981485
  • White HK et al. Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab 2009. PMID 19174493
  • Beck DE et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus. Int J Colorectal Dis 2014. PMID 25331030
  • Drugs@FDA record for EGRIFTA (tesamorelin), BLA 022505, original approval 2010-11-10.
  • WADA Prohibited List, section S2.2.
  • PubMed and ClinicalTrials.gov record counts retrieved 2026-09-08.

Frequently asked questions

What is a growth hormone secretagogue?

It is a compound that causes the pituitary gland to release more of the body's own growth hormone, rather than supplying growth hormone from outside. Two different mechanisms sit under the one label. GHRH analogues copy growth hormone releasing hormone, the natural signal from the hypothalamus; ghrelin-receptor agonists copy ghrelin, the hunger signal, which acts on a separate receptor and also drives GH release. Both raise GH. They do it through different doors, which is why they are sometimes sold as a pair.

Do growth hormone secretagogues build muscle?

They raise growth hormone and IGF-1, and that part is not in dispute — it has been measured repeatedly. Whether the raised hormone becomes contractile muscle is a separate question, and the trials that asked it directly returned modest answers. The best-evidenced compound in the class added about a kilogram of fat-free mass over a year in older adults and produced no measurable strength or function gain. No trial in this class has ever been run in trained adults doing resistance training, which is the population buying them.

Is any growth hormone secretagogue FDA-approved?

Tesamorelin is. It was approved in November 2010 as EGRIFTA and is a GHRH analogue, so it belongs squarely in this class. Its approved indication is the reduction of excess abdominal fat in people with HIV-associated lipodystrophy. That is the entire scope of the approval — a fat-distribution indication in a specific clinical population, not a muscle indication and not a performance indication. Every other secretagogue sold direct to consumers is an unapproved drug.

Why is fat-free mass not the same as muscle?

Fat-free mass is everything in the body that is not fat, and that includes water. Growth hormone causes fluid retention, which is why mild swelling of the lower legs is a recurring adverse event in these trials. A scan showing more fat-free mass after a secretagogue is therefore consistent with more muscle, more water, or both, and the trials that tried to separate the two using intracellular water found the cell-mass change smaller than the fat-free-mass change. This is the single most useful thing to know when reading a marketing claim built on a body-composition number.

Are these compounds detectable in a drug test?

Yes, and the analytical literature on catching them is larger than the clinical literature on whether they work. Published methods cover GHRP-1, GHRP-2, GHRP-6, hexarelin and ipamorelin in urine, including after nasal administration, and separate methods exist for the GHRH analogues in plasma. WADA prohibits the class at all times under S2.2, so an out-of-competition test is in scope. Our page on peptides and drug testing carries the per-compound detail.

Which compound in this class has the best human evidence?

MK-677, and it is not close — 18 randomised trials against ipamorelin's 2 and CJC-1295's none. It is also not a peptide, which is the awkward part of the answer for a category usually sold as one. Ranking by evidence rather than by marketing puts an oral small molecule first, a veterinary appetite stimulant second, and the injectable peptides that dominate the market well below both.