Ipamorelin

Ipamorelin is a synthetic peptide of five amino acids that makes the pituitary gland release growth hormone. It was designed at Novo Nordisk and described in 1998 as "the first selective growth hormone secretagogue": in animals it released growth hormone without raising cortisol, a side effect of the related peptides known at the time[1].

That selectivity, shown in rats and pigs, is the basis of its reputation. The human evidence is thin. Only two peer-reviewed studies in people have been published: a pharmacokinetic study in healthy men in 1999[2] and a phase 2 trial in patients after bowel surgery in 2014, which did not meet its goal[3]. Ipamorelin is not an approved medicine, an FDA advisory committee voted in 2024 against adding either form to the section 503A Bulks List for pharmacy compounding[4], and WADA bans it in sport[5].

How it was designed

Ipamorelin came out of a medicinal chemistry programme on growth hormone-releasing peptides (GHRPs), small synthetic peptides that stimulate growth hormone through a receptor of their own. The starting point was GHRP-1, a seven-residue peptide that already contained two D-amino acids[1].

The Novo Nordisk chemists first removed the central Ala-Trp. The shorter peptide kept most of its activity in rat pituitary cells. Replacing the first L-alanine with its mirror image, D-alanine, made the peptide clearly weaker. Replacing it with Aib, an amino acid with two methyl groups on the α-carbon and therefore no L or D form, restored the potency of GHRP-1: the concentration giving half the maximal effect was 1.3 nmol/L for ipamorelin and 1.1 nmol/L for GHRP-1[1]. The result is a pentapeptide in which three of the five residues are not standard L-amino acids: Aib, D-2-Nal and D-Phe. 2-Nal, with its naphthalene ring, is a noncanonical amino acid, as is Aib.

For a chemist, the series makes a simple point: configuration matters. L-alanine and D-alanine contain the same atoms and differ only in the arrangement around one carbon, yet swapping one for the other at position 1 clearly weakened the peptide[1].

How it works

Ipamorelin does not act on the GHRH receptor used by sermorelin and tesamorelin. In rat pituitary cells its effect was blocked by GHRP receptor antagonists but not by a GHRH antagonist, the same pattern as for GHRP-6[1]. This receptor was cloned in 1996, and its natural ligand, the stomach hormone ghrelin, was identified in 1999[6]; ipamorelin is therefore described as a ghrelin receptor agonist or ghrelin mimetic[3].

The property that made ipamorelin interesting was selectivity. In conscious pigs, GHRP-6 and GHRP-2 raised ACTH and cortisol as well as growth hormone. Ipamorelin did not raise them above the levels seen after GHRH, even at doses more than 200 times higher than the dose giving half the maximal growth hormone response. None of the peptides changed FSH, LH, prolactin or TSH[1]. This was shown in animals; the two published human studies did not report cortisol, so the selectivity has not been confirmed in people.

Animal studies

• Bone growth in rats (1999). Adult female rats were injected three times a day for 15 days. The bone growth rate in the tibia rose with the dose, from 42 µm per day without treatment to 52 µm per day at the highest dose, and body weight increased. IGF-1 levels did not change[7].
• Repeated dosing in young rats (2002). Daily injections for 21 days increased weight gain. Pituitary cells taken from the treated rats still responded to ipamorelin and GHRH, while cells from rats pretreated with GHRH responded less, which the authors interpreted as an absence of desensitisation with ipamorelin[6].

Both studies were short, used rats, and measured growth and hormone release, not health outcomes. The authors of the 1999 study wrote that any use in children with growth retardation would have to be demonstrated in clinical studies[7].

Studies in people

Pharmacokinetics in healthy men (1999). Healthy men aged 25 to 41 received a 15-minute intravenous infusion of ipamorelin at one of five doses, with six men per dose and two on placebo. The peptide behaved predictably: blood levels rose in proportion to the dose, and the half-life was about 2 hours. Each dose produced a single burst of growth hormone, peaking about 40 minutes after the start of the infusion and falling to very low levels by 6 hours, even though ipamorelin itself was still in the blood[2]. The study was done with an intravenous formulation and did not test injections under the skin, repeated dosing or effects on the body.

The article gives the terminal half-life as "about 2 h" in its abstract and discussion and as "about 1 h" in the results section; the page uses the figure from the abstract.

Phase 2 trial after bowel surgery (2014). Because ghrelin receptor stimulation speeds up the gut, ipamorelin was tested as a treatment for postoperative ileus, the temporary paralysis of the bowel after abdominal surgery. In a double-blind trial sponsored by Helsinn Therapeutics, 117 patients were enrolled after bowel resection, and 114 were included in the safety and efficacy analyses. They received intravenous ipamorelin 0.03 mg/kg or placebo twice a day for up to 7 days[3].

56 patients on ipamorelin, 58 on placebo. None of the differences was statistically significant (main outcome p = 0.15). Data from Beck et al. (2014)[3].

Serious adverse events occurred in 17.9% of patients on ipamorelin and 15.5% on placebo. Two patients on ipamorelin died after complications of the bowel surgery, and none on placebo. The paper reports that the investigators classed both deaths as possibly related to the study drug, without further explanation. Low blood potassium was reported more often with ipamorelin (12.5% vs 3.4%), and more patients on ipamorelin moved from normal to high blood glucose by discharge (14.3% vs 8.6%)[3]. Two earlier phase 1 studies mentioned in the paper have not been published[3].

Safety and regulatory status

Ipamorelin is not an approved medicine, and US regulators have looked at it twice in the context of compounding. Since September 2023 ipamorelin acetate has been in category 2 of the FDA's interim list for outsourcing facilities (section 503B): bulk substances that may present significant safety risks. The agency cited the serious adverse events, including death, reported when ipamorelin was given intravenously to improve gut motility, the risk of immune reactions from aggregation or peptide impurities, and the difficulty of characterising a peptide that contains non-natural amino acids. It also stated that it had not identified safety information for some other injection routes[8].

Separately, in October 2024 the FDA reviewed ipamorelin and ipamorelin acetate for the list of substances that ordinary pharmacies may use for compounding (section 503A), for growth hormone deficiency and postoperative ileus. FDA staff concluded that the evaluation criteria weighed against including either form[9]. On 29 October 2024 the Pharmacy Compounding Advisory Committee agreed: for each form the vote was 0 in favour, 12 against and 1 abstention, with members citing a lack of information supporting safety and efficacy[4].

Ipamorelin is prohibited in sport at all times. WADA lists it by name among the growth hormone secretagogues in class S2[5].

References

1. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology 139(5):552–561. DOI: 10.1530/eje.0.1390552
2. Gobburu JVS, Agersø H, Jusko WJ, Ynddal L (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical Research 16(9):1412–1416. DOI: 10.1023/A:1018955126402
3. Beck DE, Sweeney WB, McCarter MD, on behalf of the Ipamorelin 201 Study Group (2014). Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. International Journal of Colorectal Disease 29(12):1527–1534. DOI: 10.1007/s00384-014-2030-8
4. U.S. Food and Drug Administration (2025). Final summary minutes of the Pharmacy Compounding Advisory Committee meeting, 29 October 2024. fda.gov (PDF)
5. World Anti-Doping Agency (2025). The 2026 Prohibited List, International Standard. wada-ama.org
6. Jiménez-Reina L, Cañete R, de la Torre MJ, Bernal G (2002). Chronic in vivo ipamorelin treatment stimulates body weight gain and growth hormone (GH) release in vitro in young female rats. European Journal of Anatomy 6(1):37–45.
7. Johansen PB, Nowak J, Skjærbæk C, Flyvbjerg A, Andreassen TT, Wilken M, Ørskov H (1999). Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Hormone & IGF Research 9:106–113.
8. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Content current as of 22 April 2026. fda.gov
9. U.S. Food and Drug Administration (2024). FDA evaluation of ipamorelin-related bulk drug substances (ipamorelin (free base) and ipamorelin acetate). Briefing document for the Pharmacy Compounding Advisory Committee meeting of 29 October 2024. fda.gov (PDF)