Growth hormone secretagogues

Ipamorelin

Plain-English version: A five amino acid peptide that switches on the same receptor the hunger hormone ghrelin uses, prompting the pituitary to let go of growth hormone.

Strongest evidence, and what it covers [Human RCT] growth hormone release and postoperative gastrointestinal recovery [1] [2] [3] [25]

Ipamorelin is five amino acids long and acts at the growth hormone secretagogue receptor. Its distinguishing published result is about what it leaves alone. In conscious swine it released growth hormone with a potency close to GHRP-6, and none of the secretagogues tested moved FSH, LH, prolactin or TSH. GHRP-6 and GHRP-2 raised ACTH and cortisol in the same animals; ipamorelin did not, at exposures more than two hundred times the level that released growth hormone [1]. That comparison was run in pigs and rats, by the laboratory that developed the compound, and it is the origin of every selectivity claim made for this molecule.

The human record is one completed trial, and it is about the gut. Three registrations exist, two of them phase 2 in postoperative ileus. The published one enrolled 117 adults having open or laparoscopic bowel resection across multiple centres, double blind against placebo, with 114 in the analysis population. Median time to tolerating a standardised solid meal was 25.3 hours against 32.6 hours on placebo, which did not reach significance (p equals 0.15), and no secondary efficacy analysis separated the arms either [2]. Nothing has been registered or published on body composition, recovery or ageing.

Where it stands FDA reviewed ipamorelin acetate and ipamorelin free base at the Pharmacy Compounding Advisory Committee meeting of 29 October 2024, for growth hormone deficiency and postoperative ileus, under Federal Register document 2024-21241 and docket FDA-2024-N-4188 [3]. It is not an approved drug in the United States and it is not on the 503A Bulks List. WADA's 2026 Prohibited List reaches growth hormone secretagogues under class S2, prohibited at all times [25].

Our takeThe selectivity finding is genuine and it is in pigs. The only completed human trial of this molecule asked whether it got a bowel moving faster after surgery, and what it returned was a gap of seven hours that did not reach significance.

• How this site grades a claim, tier by tier

CJC-1295 without DAC

Also known as Mod GRF 1-29, Modified GRF

Plain-English version: A 29 amino acid copy of the hormone that tells the pituitary to release growth hormone, with four changes that make it last longer than the natural version.

Strongest evidence, and what it covers [Anecdote] growth hormone release from a modified releasing hormone fragment [4] [5] [24]

This is growth hormone releasing hormone 1-29 with four amino acid substitutions that slow the enzymes which clear it. It is sold as Mod GRF 1-29 and as modified GRF, and it is the default partner to ipamorelin in blended products. The substitutions are the whole difference between it and sermorelin, and the linker is the whole difference between it and CJC-1295 with DAC.

Searching the published literature for a study of this exact molecule returns nothing. The two human pharmacology studies published under the CJC-1295 name both used the albumin-binding version [4] [5], and the single registration under that name is that version's terminated phase 2. Duration, potency and pulse-pattern claims made for the no-DAC form therefore trace to vendor and community sources rather than to a study of the compound being sold, which is the tier this entry carries. A 2018 review of the class reaches the same position on the growth hormone releasing peptides sold without registered trials behind them [24].

Where it stands Unapproved in the United States and everywhere else, with no registration of its own on ClinicalTrials.gov as of 2 August 2026. WADA's 2026 Prohibited List reaches growth hormone releasing hormone analogues under class S2, prohibited at all times [25].

Our takeOne base molecule is sold as two products and only one of them has been studied in a person. Every figure quoted for this version, on how long it lasts and on how it shapes a pulse, came off the other one.

• The version that was studied in people, and what it measured

CJC-1295 with DAC

Also known as Drug Affinity Complex, CJC-1295 DAC

Plain-English version: The same 29 amino acid molecule as CJC-1295, with a linker attached that ties it to a blood protein so it circulates for days rather than minutes.

Strongest evidence, and what it covers [Human RCT] sustained growth hormone and IGF-1 elevation in healthy adults [4] [5] [6] [25]

DAC stands for Drug Affinity Complex. It is a chemical group that bonds the peptide to albumin, the most abundant protein in blood, so the molecule is carried around instead of being cleared. The base peptide is identical to the entry above; the linker is the product difference, and it is the reason this version has a published human pharmacology record while the other does not.

Teichman and colleagues ran two randomised, placebo-controlled, double-blind ascending studies in healthy adults aged 21 to 61, over 28 and 49 days, given subcutaneously. After a single administration, mean plasma growth hormone rose 2 to 10 fold for six days or more and mean IGF-1 rose 1.5 to 3 fold for nine to eleven days. The estimated half-life of the compound was 5.8 to 8.1 days, and after repeated administration mean IGF-1 stayed above baseline for as long as 28 days [4]. Those are concentration measurements in blood. No body composition, strength or clinical endpoint was measured in either study.

A second group then asked what the pattern of release looked like, because pulsing matters for how growth hormone acts. Sampling every 20 minutes across a 12 hour overnight window in healthy men aged 20 to 40, before and one week after a single administration, they found the frequency and the magnitude of growth hormone pulses unaltered, and reported that pulsatile secretion persists under continuous stimulation. What changed was the floor between the pulses: trough growth hormone rose 7.5 fold, mean growth hormone rose 46 percent and IGF-1 rose 45 percent [5]. These two papers are usually cited one at a time and they point in different directions for the argument people are having. One is used to say the compound produces a flat, sustained elevation unlike anything the body does; the other reports the pulses still there. Both are on this page because both were measured, and the reading that fits them together is that the pulses continued while the baseline underneath them was lifted several fold.

The programme did not continue. NCT00267527, a multicentre randomised double-blind placebo-controlled phase 2 in HIV-associated visceral obesity, ran from December 2005 with a listed enrolment of 120 and a listed completion of September 2006. The registry records it as terminated, gives no reason, and carries no posted results, and no paper reporting it has been published [6]. Nothing has been registered under this name since.

Where it stands Unapproved in the United States. Its only registration is the terminated phase 2 above [6]. WADA's 2026 Prohibited List reaches growth hormone releasing hormone analogues under class S2, prohibited at all times [25].

Our takeThis is the best characterised molecule in the group and the characterisation stops at a blood concentration. A compound can lift growth hormone for a week and still have never been measured against an outcome anyone cares about, and that is exactly where this record ended.

• The version sold as Mod GRF 1-29, and why its evidence is not this evidence

Sermorelin

Also known as GRF 1-29, Geref

Plain-English version: The first 29 amino acids of the hormone that tells the pituitary to release growth hormone, once sold as an approved medicine in the United States.

Strongest evidence, and what it covers [Human open-label] growth hormone release in growth hormone deficiency [7] [8] [9] [24]

Sermorelin is growth hormone releasing hormone 1-29, unmodified, and it carries the most registrations in this group: 42 on ClinicalTrials.gov as of 2 August 2026. It held two US approvals under the name Geref, one from December 1990 for evaluating whether a pituitary can secrete growth hormone, and one from September 1997 for growth hormone deficiency in children with growth failure [8]. The adult body composition and ageing use it is sold for now has never been tested in a trial of this molecule. The ageing study usually cited for it administered [Nle27] growth hormone releasing hormone 1-29, a substituted analogue, and under this site's rules that result stays with that molecule [9] [24].

The human record that does exist is paediatric and open label. One hundred and ten previously untreated prepubertal children with growth hormone deficiency were treated for up to a year across multiple centres with no control arm, 86 of them eligible for the efficacy analysis. Mean height velocity rose from 4.1 cm per year at baseline to 8.0 at six months and 7.2 at twelve [7]. That is a growth endpoint, in children whose pituitaries were failing, measured without a comparator.

Where it stands The application holder notified FDA during 2008 that both Geref products were being discontinued, and FDA withdrew approval of NDA 19-863 and NDA 20-443 effective 18 June 2009. In 2013, acting on a citizen petition, FDA determined that neither product had been withdrawn for reasons of safety or effectiveness, which is the finding that lets a generic application reference them (Federal Register document 2013-04827, docket FDA-2012-P-1071) [8]. There has been no approved sermorelin product in the United States since 2009.

Our takeForty-two registrations look like the strongest record in the category until you read what they asked. They asked whether a pituitary is functioning and whether a short child grows. Neither question is the one this compound is now sold to answer.

• Mod GRF 1-29, the near-name that is a different molecule

Tesamorelin

Also known as Egrifta, TH9507

Plain-English version: A stabilised copy of the full growth hormone releasing hormone, and the only compound on this page that is an approved drug substance.

Strongest evidence, and what it covers [Human RCT] visceral fat reduction in HIV-associated lipodystrophy [10] [11] [12] [23] [25]

Tesamorelin is the 44 amino acid releasing hormone with a chemical group at the front end that slows its breakdown [11]. It is the only compound here with a completed phase 3 programme, and that programme asked one question in one population.

Two multicentre, double-blind, placebo-controlled phase 3 trials were pooled: 806 people on antiretroviral therapy with HIV and excess abdominal fat, randomised two to one, 26 weeks of daily subcutaneous treatment then a 26 week extension. Visceral adipose tissue measured by CT fell by 24 square centimetres against a rise of 2 on placebo, a treatment effect of 15.4 percent, while abdominal subcutaneous fat did not change significantly [11]. An earlier phase 3 found the same direction [10], and a later randomised trial measured hepatic fat and liver histology in HIV-associated fatty liver disease [12].

Every participant was living with HIV, and the population is not incidental: HIV-associated lipodystrophy is a specific pattern of fat redistribution rather than ordinary abdominal fat. No trial has tested tesamorelin for fat loss or ageing in anyone else. A vial sold under a research-use-only label holds a drug substance with an approved US application, and the label does not change the molecule [23].

Where it stands Approved in the United States as EGRIFTA under application BLA 022505, originally approved on 10 November 2010, for a specific HIV-associated indication [23]. WADA's 2026 Prohibited List reaches growth hormone releasing hormone analogues under class S2, prohibited at all times [25].

Our takeThe strongest evidence on this page and the narrowest question. Eight hundred people, a hard imaging endpoint and a real effect size, all of it inside one diagnosis, which is precisely the gap between what the trials established and what is being sold.

• Compounds studied for fat loss, and what each trial measured

Hexarelin

Also known as Examorelin

Plain-English version: A six amino acid peptide at the same receptor as ipamorelin, producing the largest growth hormone pulse of the group.

Strongest evidence, and what it covers [Human open-label] growth hormone release, body composition and cardiac effects [13] [14] [15] [24]

Hexarelin has never been entered into a registered trial: the ClinicalTrials.gov count on 2 August 2026 is zero under both its names. What exists instead is a body of small Italian and British pharmacology work from the 1990s, and it is more informative than the registration count suggests. A 1994 comparison gave the compound by four routes in man, intravenous, subcutaneous, intranasal and oral, and reported the growth hormone response falling off sharply from the injected routes to the oral one [14].

The study that matters most for how it is sold ran 16 weeks of continuous subcutaneous administration in adults, with the growth hormone response re-measured at intervals and again four weeks after stopping. The area under the growth hormone curve was 19.1 at week 0, 13.1 at week 1, 12.3 at week 4 and 10.5 at week 16, a significant decline across the study period. Four weeks after the last administration it was 19.4, significantly higher than at week 16 and not significantly different from where it started [13]. So the response to hexarelin wears down while it is being taken and comes back when it stops. The authors described the attenuation as partial and reversible, which is what the numbers show.

The same study measured the endpoints people buy this compound for, and they did not move. Serum IGF-1 and IGF binding protein 3 were unchanged across the 20 weeks. Total body fat, lean body mass and bone mineral density were unchanged at week 16 against baseline. Of the bone turnover markers, only the C-terminal propeptide of type I collagen changed significantly [13]. A single-arm study of that size cannot rule an effect in or out, and it is also the only long study of this compound that anyone has published.

The cardiovascular claims made for hexarelin are preclinical. The most-cited experiment gave it to rats after an experimental myocardial infarction and reported changes in cardiac function against untreated animals [15]. There is no human cardiac trial of this compound, and the receptor work behind those experiments is itself contested, because binding sites in heart tissue are not the same population as the pituitary receptor. Mechanism in rats does not establish an effect in people.

Where it stands Unapproved everywhere and never marketed. It has no registration on ClinicalTrials.gov under hexarelin or examorelin as of 2 August 2026. WADA's 2026 Prohibited List reaches growth hormone secretagogues under class S2, prohibited at all times [25].

Our takeThe one long human study of this compound is also the one that reports its effect fading, and it measured fat, lean mass and bone density without finding a change in any of them. That is a more useful piece of evidence than the zero in the registration column suggests.

• Why a single-arm study earns the tier it earns

GHRP-2

Also known as Pralmorelin

Plain-English version: A six amino acid peptide at the ghrelin receptor, used in Japan as a one-off test of whether the pituitary can release growth hormone.

Strongest evidence, and what it covers [Human open-label] growth hormone release measured as a diagnostic response [16] [24]

GHRP-2 has zero registrations on ClinicalTrials.gov under either of its names, and it is not a treatment anywhere. It is a diagnostic agent in Japan, given once, to answer a yes or no question about a pituitary. Everything published about it in people was built for that purpose.

The validation study enrolled 77 healthy subjects and 58 patients whose peak growth hormone was below 3 micrograms per litre on the insulin tolerance test, the reference method. After an overnight fast and a single intravenous administration, blood was sampled for two hours. Growth hormone peaked within 60 minutes in every subject, and repeated testing was reproducible. The responses were slightly lower in older and heavier subjects without changing the diagnosis [16].

Then the number that matters for the way this compound is marketed. Peak growth hormone reached 1.36 micrograms per litre in the patients and 84.6 in the healthy group, a difference of better than sixty fold and significant at p below 0.001 [16]. That gap is what makes it a usable test: a pituitary that is failing barely responds to GHRP-2, while a healthy one responds enormously. A compound sold on the premise of restoring a declining growth hormone axis produces its smallest response in the people whose axis has actually declined, and its largest in people whose axis is intact.

What that leaves untested is everything else. A single provocative administration in a clinic is not a course of treatment, and no study has followed anyone taking GHRP-2 for weeks. Body composition, strength, recovery, sleep and ageing have not been measured for this compound in any published human work, and the class review reaches the same conclusion [24]. The comparison people actually want, GHRP-2 against ipamorelin on cortisol, rests on the swine pharmacology in the ipamorelin entry above rather than on a human head to head, because no human head to head exists.

Where it stands Not approved in the United States and not on the 503A Bulks List. Its approval in Japan is as a diagnostic agent for growth hormone deficiency rather than as a therapy. WADA's 2026 Prohibited List reaches growth hormone secretagogues under class S2, prohibited at all times [25].

Our takeThe diagnostic literature is real human data and it cuts against the sales pitch rather than for it. A response that collapses in exactly the population the marketing describes is not a footnote, it is the finding.

• Ipamorelin, the compound GHRP-2 is compared with on cortisol

GHRP-6

Plain-English version: A six amino acid peptide at the ghrelin receptor whose most reliably documented effect is a sharp rise in hunger.

Strongest evidence, and what it covers [Human RCT] overnight growth hormone, ACTH and cortisol release, and sleep architecture [17] [18] [19] [24]

GHRP-6 has zero registrations on ClinicalTrials.gov. It is one of the original growth hormone releasing peptides, characterised in the 1990s alongside hexarelin and GHRP-2, and most of what has been published about it since is animal work on tissue protection rather than anything about the uses it is sold for.

The appetite effect that defines its reputation was established in rats, and the design is worth naming. GHRP-6 was delivered directly into the brain ventricles, which stimulated eating without affecting plasma growth hormone responses [18]. Two things follow. The feeding effect and the growth hormone effect were separable in that model, so one is not evidence for the other. And the route was intracerebroventricular, not a route anyone uses, which is the single largest gap between that experiment and a person. No published human study measuring appetite after GHRP-6 could be found for this page, so the widely repeated claim about how quickly hunger arrives rests on community reports.

One human pharmacokinetic study exists. Nine healthy men received a single intravenous administration at three levels, with the peptide measured in plasma by mass spectrometry. Disposition fitted a two-compartment model, giving a distribution half-life of about 7.6 minutes and an elimination half-life of about 2.5 hours [19]. That is a description of how fast the molecule leaves, and nothing else.

The one controlled human study of what it does is indexed by PubMed as a randomised controlled trial, and it compared repetitive intravenous boluses against placebo in healthy men, with hormones sampled from 20.00 to 07.00 and sleep recorded by EEG. Growth hormone rose, and so did ACTH and cortisol across the first half of the night, which is the opposite direction to what growth hormone releasing hormone does to cortisol. Stage 2 sleep increased while slow wave sleep did not change [17]. That cortisol result is the measured basis for the selectivity comparison the ipamorelin entry describes, and it is one small study in healthy men.

Where it stands Unapproved everywhere, with no registration on ClinicalTrials.gov as of 2 August 2026 and no diagnostic approval of the kind GHRP-2 holds in Japan. WADA's 2026 Prohibited List reaches growth hormone secretagogues under class S2, prohibited at all times [25].

Our takeThe best-documented thing this compound does in a person is raise cortisol overnight, and the effect it is famous for was shown in rats that received it straight into the brain ventricles. Those two sentences are the whole honest summary.

• How a route difference changes what a study can show

MK-677

Also known as Ibutamoren, Nutrobal, MK-0677

Plain-English version: Not a peptide. A small molecule taken by mouth that acts at the ghrelin receptor, developed by a major manufacturer and then abandoned.

Strongest evidence, and what it covers [Human RCT] body composition and metabolic effects of an oral ghrelin mimetic [3] [20] [21] [22] [26]

MK-677 is an orally active ghrelin mimetic and it is not a peptide, which matters for how it is regulated and how it behaves. It carries eight registrations and the largest completed trial record here, and what those trials found is why it is not on the market.

The two-year randomised, double-blind, placebo-controlled trial in 65 healthy adults aged 60 to 81 is the one cited. Fat-free mass rose by 1.1 kg against a fall of 0.5 kg on placebo, and body weight rose by 2.7 kg against 0.8. Abdominal visceral fat and total fat mass did not differ between groups. Fasting blood glucose rose 0.3 mmol per litre on average, insulin sensitivity fell, and cortisol rose. The gain in fat-free mass produced no change in strength or function [20].

The other two completed programmes both missed. In 563 patients with mild to moderate Alzheimer's disease over 12 months, IGF-1 rose 72.9 percent and none of four endpoints separated from placebo [21]. In 161 patients recovering from hip fracture, IGF-1 rose 84 percent with no significant difference in functional performance [22]. A further phase 2 in post-fracture sarcopenia enrolled 83 and is listed as terminated, no reason recorded [26].

Where it stands FDA reviewed ibutamoren mesylate at the Pharmacy Compounding Advisory Committee meeting of 29 October 2024, for growth hormone deficiency, osteoporosis, hip fracture, sarcopenia, obesity and Alzheimer's disease, under Federal Register document 2024-21241 and docket FDA-2024-N-4188 [3]. It is not an approved drug anywhere and it is not on the 503A Bulks List. WADA's 2026 Prohibited List reaches growth hormone secretagogues under class S2, prohibited at all times [25].

Our takeThis is the compound with the answers, and that is the problem with it. Two years of randomised data produced more lean mass, no more strength, higher fasting glucose and lower insulin sensitivity, and two separate outcome programmes returned nothing.

• Compounds where glucose and insulin endpoints are the story