Ipamorelin, GHRP-2, and GHRP-6 all activate the growth hormone secretagogue receptor (GHS-R1a) — the same receptor the stomach-derived hormone ghrelin uses to stimulate growth hormone (GH) release from the pituitary [1][2]. GHRP-6 came first, developed in the 1980s; GHRP-2 followed as a more potent analog; ipamorelin came later, from a Novo Nordisk program that screened all three compounds against each other in the same experiments. That screen, published by Raun and colleagues in 1998, is the rare case in this library where a direct comparative study exists rather than only separate trials to infer across [3]. It found a real pharmacological difference — hormonal selectivity — that is the organizing fact of this comparison.
This page is not a guide to using any of these compounds. GHRP-2 and GHRP-6 have no dedicated research overview on this site because they are not sold here; everything about them below is drawn fresh from the published literature, cited independently of the site's existing ipamorelin coverage. For full single-compound detail on ipamorelin — including its human pharmacokinetic data and its discontinued postoperative-ileus clinical trial — see the dedicated article on ipamorelin.
Side-by-Side Overview
| Ipamorelin | GHRP-2 | GHRP-6 | |
|---|---|---|---|
| Structure/class | Synthetic pentapeptide GHS-R1a agonist (Aib-His-D-2-Nal-D-Phe-Lys-NH2) [3] | Synthetic hexapeptide GHS-R1a agonist, developed as a more potent analog within the GHRP series [8] | Synthetic hexapeptide GHS-R1a agonist; the first compound described in the GHRP series [4] |
| GHS-R1a activity | Full agonist; GH-releasing potency/efficacy comparable to GHRP-6 in vitro and in vivo [3] | Full agonist; more potent but less efficacious than GHRP-6 or ipamorelin on GH release, in the direct three-way comparison [3] | Full agonist; the reference compound against which ipamorelin and GHRP-2 were benchmarked [3][4] |
| Hormonal selectivity (headline finding) | Did not raise ACTH or cortisol above GHRH-alone levels, even at doses over 200-fold above its half-maximal GH-releasing dose [3] | Raised plasma ACTH and cortisol in the same porcine comparison [3]; a separate human study found it raised GH, prolactin, ACTH, and cortisol together [5] | Raised plasma ACTH and cortisol in the same porcine comparison [3] |
| Appetite effects | No dedicated appetite-stimulation study located; a 2024 ferret study tested it for limiting chemotherapy-associated weight loss, not for driving hunger in healthy subjects [14] | Rat food-intake findings [6] and a small controlled human meal-intake study [15] | Increased weight gain and visceral fat accrual in rats, with the effect size depending on insulin/glucose status [7]; no verified human hunger-scale study located |
| Human data status | One human PK/PD dose-escalation study (n=40) [12]; one completed phase 2 efficacy trial that did not meet its endpoints [13] | In clinical diagnostic use in Japan as the "GHRP-2 test" for adult GH deficiency [11]; no verified randomized human efficacy trial as a therapeutic agent | No verified controlled human efficacy or diagnostic-approval literature located |
| Development history | Developed by Novo Nordisk in the 1990s; reached a phase 2 trial for postoperative ileus that did not meet its endpoint [3][13] | Developed to improve on GHRP-6's potency; a 2004 industry drug profile describes a US therapeutic program for short stature as discontinued while Japanese diagnostic development continued [9] | First described in rat pituitary cell and whole-animal studies in 1984 [4] |
The Discovery Lineage: GHRP-6 to GHRP-2 to Ipamorelin
GHRP-6 is the compound that started this pharmacological class. Bowers and colleagues first described it in 1984, reporting that a synthetic hexapeptide acted directly on the pituitary to release GH in rat cell cultures and in whole animals, through a mechanism distinct from growth hormone-releasing hormone (GHRH) [4]. Over the following decade, Bowers' group and collaborators characterized a series of structural analogs aimed at improving GH-releasing potency; GHRP-2 emerged from that program as a hexapeptide with greater potency per dose than GHRP-6, described in Bowers' own 1993 review of the series' structure-activity relationships [8]. The human endocrine comparison cited here measured GH alongside prolactin, ACTH and cortisol [5]; the separate 2004 source describes pralmorelin’s development history [9].
Ipamorelin came out of a different laboratory a decade after GHRP-6. Novo Nordisk researchers built it by removing a central dipeptide from an earlier GHRP-1 scaffold, then tested the resulting pentapeptide directly against GHRP-6 and GHRP-2 in the same experimental systems — rat pituitary cell cultures, anesthetized rats, and conscious pigs [3]. That head-to-head design is what makes the Raun 1998 paper unusual in this literature: it is a genuine controlled comparison of all three compounds, not three separate studies compared after the fact.
The Published Selectivity Comparison
In the Raun 1998 pig experiments, all three peptides released GH, with GHRP-2 more potent (effective at a lower dose) but less efficacious (a lower maximum GH output) than either GHRP-6 or ipamorelin, which behaved similarly to each other on the GH measure alone [3]. The distinguishing result came from the hormone-specificity panel run alongside the GH measurements: GHRP-6 and GHRP-2 both raised plasma ACTH and cortisol, while ipamorelin did not raise either hormone to a level significantly different from GHRH stimulation alone, even at doses more than 200-fold above what was needed for half-maximal GH release. None of the three peptides affected FSH, LH, prolactin, or TSH in that pig model [3]. That is the specific, numbered basis for describing ipamorelin as pharmacologically "selective" relative to GHRP-2 and GHRP-6 — a single animal study, not a finding repeated across independent laboratories, but one that directly compared all three compounds side by side.
Human data point the same direction for GHRP-2, independently of the Raun comparison. Arvat and colleagues gave GHRP-2 and the related hexapeptide hexarelin to healthy volunteers and reported that both produced a GH response larger than GHRH alone, while also raising prolactin, ACTH, and cortisol — the endocrine pattern the Raun pig study had already found for GHRP-2 [5]. An equivalent human hormone-panel study of GHRP-6 specifically was not located for this article; the GHRP-6 selectivity data above rests on the porcine comparison rather than an independent human trial.
Appetite and Ghrelin-Mimetic Effects
Because all three compounds act at the same receptor as ghrelin, and ghrelin itself has a documented appetite-stimulating effect in humans — infusion raised hunger ratings and food intake at a subsequent meal in a controlled trial [10] — GHRP-2 and GHRP-6 have each been studied separately for orexigenic (appetite-driving) activity, mostly in rodents. Central administration of GHRP-2 (studied under its research code KP-102) increased food intake in free-feeding rats when delivered directly into the brain, alongside GHRH, pointing to a hypothalamic site of action distinct from the pituitary [6]. GHRP-6 produced weight gain and increased visceral fat mass in a rat model, with the size of the effect depending on the animals' insulin and glucose status [7]. A controlled study in seven healthy men found greater buffet-meal intake during GHRP-2 exposure than during saline exposure [15]. It is a small, acute experiment, not evidence of long-term benefit. The cited GHRP-6 appetite/fat-mass findings remain animal data, and the ipamorelin ferret study addresses chemotherapy-associated weight loss [14].
Clinical-Development Fates
The three compounds' paths through drug development diverged sharply. Ipamorelin reached a completed phase 2 randomized trial in bowel-surgery patients that did not meet its efficacy endpoints, and its development for that indication appears to have ended there — see the ipamorelin research article for the full trial detail [13]. GHRP-2, marketed and studied under the name pralmorelin, took a different route: a 2014 review of adult GH deficiency testing describes the GHRP-2 test as an available, recommended GH-stimulation diagnostic in Japan, used against an established peak-GH cutoff to identify severe adult GH deficiency [11]. A 2004 industry drug-development profile separately describes an earlier US phase 2 program studying GHRP-2 as a potential treatment for short stature as discontinued by its original developer, while a Japanese licensee continued both diagnostic and therapeutic development there [9]. No equivalent regulatory diagnostic or therapeutic history for GHRP-6 was located in the literature reviewed for this article; on the evidence gathered here, it remains a research compound without a documented clinical-approval record of its own.
What Has No Human Data
To be explicit about the gaps: GHRP-6's appetite and fat-mass findings are rat data, not human [7]. Ipamorelin's selectivity finding itself comes from cell cultures, rats, and pigs, not humans — its separate human data covers only GH-release PK/PD, not hormone specificity [3][12]. No source located for this article reports a controlled human trial comparing all three compounds directly on any outcome; the 1998 animal pharmacology study remains the only three-way comparison identified [3].
References
- Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656-660. doi:10.1038/45230 — PMID: 10604470
- Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. doi:10.1126/science.273.5277.974 — PMID: 8688086
- Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. doi:10.1530/eje.0.1390552 — PMID: 9849822
- Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. 1984;114(5):1537-1545. doi:10.1210/endo-114-5-1537 — PMID: 6714155
- Arvat E, Di Vito L, Maccagno B, Broglio F, Boghen MF, Deghenghi R, Camanni F, Ghigo E. Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH. Peptides. 1997;18(6):885-891. doi:10.1016/s0196-9781(97)00016-8 — PMID: 9285939
- Okada K, Ishii S, Minami S, Sugihara H, Shibasaki T, Wakabayashi I. Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. Endocrinology. 1996;137(11):5155-5158. doi:10.1210/endo.137.11.8895390 — PMID: 8895390
- Granado M, García-Cáceres C, Frago LM, Argente J, Chowen JA. The positive effects of growth hormone-releasing peptide-6 on weight gain and fat mass accrual depend on the insulin/glucose status. Endocrinology. 2010;151(5):2008-2018. doi:10.1210/en.2009-1394 — PMID: 20219977
- Bowers CY. GH releasing peptides--structure and kinetics. J Pediatr Endocrinol. 1993;6(1):21-31. doi:10.1515/jpem.1993.6.1.21 — PMID: 8374685
- Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. Drugs R D. 2004;5(4):236-239. doi:10.2165/00126839-200405040-00011 — PMID: 15230633
- Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86(12):5992. doi:10.1210/jcem.86.12.8111 — PMID: 11739476
- Fukuda I, Hizuka N, Muraoka T, Ichihara A. Adult growth hormone deficiency: current concepts. Neurol Med Chir (Tokyo). 2014;54(8):599-605. doi:10.2176/nmc.ra.2014-0088 — PMID: 25070016
- Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999;16(9):1412-1416. doi:10.1023/a:1018955126402 — PMID: 10496658
- Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014;29(12):1527-1534. doi:10.1007/s00384-014-2030-8 — PMID: 25331030
- Lu Z, Ngan MP, Liu JYH, Yang L, Tu L, Chan SW, Giuliano C, Lovati E, Pietra C, Rudd JA. The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism. Physiol Behav. 2024;284:114644. doi:10.1016/j.physbeh.2024.114644 — PMID: 39043357
References 3, 12, 13, and 14 above are shared with, and copied accurately from, the dedicated ipamorelin research article on this site.
- Laferrère B, et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. J Clin Endocrinol Metab. 2005;90(2):611-4. doi:10.1210/jc.2004-1719. PMID: 15699539
This article summarizes published scientific literature for educational purposes only. Ipamorelin, GHRP-2, and GHRP-6 are not approved drugs for human use in the United States; GHRP-2 (pralmorelin) has diagnostic use under separate regulatory status in Japan, described above. None of the three is an approved treatment for any condition, and this page does not describe, endorse, or recommend use of any of them in humans. Research-grade material referenced elsewhere on this site is sold for laboratory research use only and is not a drug product. Nothing here constitutes medical advice, and no statement about research materials has been evaluated by the FDA.