Monograph in Growth-hormone axis peptides
Ipamorelin
A five-residue ghrelin-receptor agonist described in 1998 as the first selective growth-hormone secretagogue — with one published human efficacy trial, which missed its endpoints.
Also called NNC 26-0161 · Ipamorelin acetate
Best evidence: Limited / early human data
One small randomized proof-of-concept trial (postoperative ileus) showed no significant benefit; the rest of the record is animal and pharmacology work.
Not FDA-approved · FDA compounding Category 2 (503B)
Residue Editorial Team · updated
What is Ipamorelin?
Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) that stimulates growth hormone release through the ghrelin (GH-secretagogue) receptor without raising other pituitary hormones in animal studies1PubMedIpamorelin, the first selective growth hormone secretagogue. Raun K et al. Eur J Endocrinol. 1998.. Its only published randomized human efficacy trial, in 114 bowel-surgery patients, found no significant benefit over placebo2PubMedProspective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE et al. Int J Colorectal Dis. 2014.. It is not FDA-approved, and FDA lists ipamorelin acetate in compounding Category 2 for outsourcing facilities3FDACertain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026..
Key findings
- Ipamorelin released GH with potency and efficacy similar to GHRP-6 in rat pituitary cells, anesthetized rats and swine1.
- In swine, it did not change FSH, LH, prolactin or TSH — the basis for calling it the first selective GH secretagogue1.
- A randomized proof-of-concept trial in 114 bowel-resection patients found median time to first tolerated meal of 25.3 versus 32.6 hours (p=0.15), with no significant differences on any efficacy analysis2.
- In rats, repeated intravenous dosing improved postoperative gut transit and food intake4PubMedEfficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. Venkova K et al. J Pharmacol Exp Ther. 2009., and subcutaneous dosing increased longitudinal bone growth5PubMedIpamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Johansen PB et al. Growth Horm IGF Res. 1999..
- FDA placed ipamorelin acetate in Category 2 for 503B outsourcing facilities on September 29, 2023, citing immunogenicity risk and a reported death with intravenous use3.
What is Ipamorelin, chemically?
| PubChem CID | 9831659 “Ipamorelin” |
|---|---|
| Formula | C38H49N9O5 |
| Molecular weight | 711.9 g/mol |
| CAS (as listed) | 170851-70-4 |
| FDA UNII | Y9M3S784Z6 |
| InChIKey | NEHWBYHLYZGBNO-BVEPWEIPSA-N |
| Length | 5 residues |
| Route in trials | Intravenous in the human trial; subcutaneous and IV in animals |
| Mechanism | Ghrelin-receptor (GH-secretagogue receptor) agonist |
- Hydrophobic
- Basic (+)
- Non-standard
How does Ipamorelin work?
Ipamorelin came out of a chemistry program building on growth-hormone-releasing peptide-1 (GHRP-1): it is a pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, lacking GHRP-1's central Ala-Trp dipeptide. Profiling with GHRP and GHRH antagonists showed it acts like GHRP-6, via a GHRP-like receptor — the receptor later identified as the ghrelin receptor1,4. Two of its five residues are non-standard (Aib and D-2-naphthylalanine), which is why PubChem's one-letter sequence (Figure 1) shows them as X.
What set it apart in 1998 was selectivity. In conscious swine, ipamorelin released GH with an ED50 of 2.3 nmol/kg without affecting FSH, LH, prolactin or TSH, leading the authors to call it the first selective GH secretagogue1.
What have studies found?
Animal pharmacology. In rat pituitary cells and anesthetized rats, ipamorelin's potency and efficacy were comparable to GHRP-61. Given subcutaneously three times daily for 15 days to adult female rats, it dose-dependently increased longitudinal bone growth (from 42 to 44, 50 and 52 µm/day) and body-weight gain without changing total IGF-15. In a rat model of postoperative ileus, repeated intravenous doses increased fecal output, food intake and weight gain4.
The human trial. That rodent work led to a randomized, placebo-controlled proof-of-concept study in bowel-resection patients. Of 117 enrolled, 114 were analyzed. Median time to first tolerated meal was 25.3 hours with ipamorelin versus 32.6 hours with placebo (p=0.15), and there were no significant differences in key or secondary efficacy analyses. The regimen — 0.03 mg/kg twice daily for up to seven days — was well tolerated. The authors noted the study was small and enrolled patients with diverse conditions2.
What is missing. We found no published controlled human trial of ipamorelin for the uses it is most often searched for, such as body composition, sleep or aging. PubMed tags only two records as clinical trials6PubMedPubMed search: (ipamorelin[tiab]). 51 records at fetch..
Is Ipamorelin FDA-approved?
| Record | Status | Source |
|---|---|---|
| FDA approval | No approved application Drugs@FDA returned no application for “Ipamorelin”. | openFDA |
| Compounding: Category 2 Ipamorelin acetate | 503B category 2 since September 29, 2023 “Compounded drugs containing Ipamorelin acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation or peptide-related impurities. Ipamorelin acetate also contains unnatural amino acids, which add to the complexity of peptide characterization. A study published in literature identified serious adverse events including death when ipamorelin was administered intravenously for improving gastric motility. FDA has not identified safety-related information regarding ipamorelin acetate via certain other injectable routes of administration. Therefore, the agency lacks sufficient information to know whether the drug would cause harm if administered to humans via those routes.” | 3 |
| Compounding: nominated, then withdrawn Ipamorelin acetate, which also appears in the table above because it is in category 2 under the 503B interim policy | Withdrawn nomination FDA still lists its safety concerns: “Compounded drugs containing Ipamorelin acetate may pose risk for immunogenicity for certain routes of administration due to the potential for aggregation or peptide-related impurities. Ipamorelin acetate also contains unnatural amino acids, which add to the complexity of peptide characterization. A study published in literature identified serious adverse events including death when ipamorelin was administered…” | 3 |
FDA's Category 2 entry for ipamorelin acetate applies to 503B outsourcing facilities and was added on September 29, 2023. The agency cites potential immunogenicity from aggregation or impurities, notes that unnatural amino acids complicate characterization, and refers to a published study reporting serious adverse events including death when ipamorelin was given intravenously for gastric motility3. It also appears on FDA's list of substances whose compounding nominations were withdrawn3.
What is still unknown?
- Any controlled human efficacy data outside postoperative ileus.
- Safety by route. FDA states it has not identified safety-related information for certain other injectable routes3.
What effects has Ipamorelin shown, by body system?
Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.
| System | What was observed | Grade |
|---|---|---|
| GH release | Dose-dependent GH release via a GHRP-like receptor in animal models1. | D |
| Gastrointestinal motility | Improved transit in a rat ileus model4; no significant effect in the human proof-of-concept trial2. | C |
| Bone growth | Longitudinal bone growth rose from 42 to 52 µm/day in adult female rats5. | D |
| Safety signal | FDA cites a published report of serious adverse events including death with intravenous administration for gastric motility3. | C |
How much research is there on Ipamorelin?
| Phase | Studies | Breakdown |
|---|---|---|
| Phase 2 | 2 | 2 completed, 0 active or recruiting, 0 stopped, 0 other |
| Observational | 1 | 0 completed, 1 active or recruiting, 0 stopped, 0 other |
Compare and continue
- CJC-1295 vs ipamorelinComparison
- Sermorelin vs ipamorelinComparison
- Tesamorelin vs ipamorelinComparison
- SermorelinGrowth-hormone axis peptides
- CJC-1295Growth-hormone axis peptides
- TesamorelinGrowth-hormone axis peptides
Questions readers ask
Is ipamorelin FDA-approved?
No. Drugs@FDA returned no application. FDA lists ipamorelin acetate in Category 2 — bulk substances that may present significant safety risks — for 503B outsourcing facilities, effective September 29, 20233.
How does ipamorelin work?
It stimulates GH release through a GHRP-like (ghrelin) receptor rather than the GHRH receptor; GHRP and GHRH antagonist profiling confirmed the pathway in the original pharmacology paper1.
Has ipamorelin been tested in humans?
Yes, in a small way. A randomized trial in 114 bowel-resection patients tested 0.03 mg/kg intravenously twice daily for up to 7 days for postoperative ileus; it was well tolerated but showed no significant efficacy2. ClinicalTrials.gov lists only a handful of studies7.
What are the side effects of ipamorelin?
In the ileus trial, treatment-emergent adverse events occurred in 87.5% on ipamorelin and 94.8% on placebo, reflecting the post-surgical setting2. FDA's Category 2 entry cites a literature report of serious adverse events including death with intravenous use3.
References
Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.
- 1 PubMed Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol 1998. PMID 9849822; doi:10.1530/eje.0.1390552.
- 2 PubMed Beck DE, Sweeney WB, McCarter MD, et al. 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. PMID 25331030; doi:10.1007/s00384-014-2030-8.
- 3 FDA Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026.
- 4 PubMed Venkova K, Mann W, Nelson R, et al. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther 2009. PMID 19289567; doi:10.1124/jpet.108.149211.
- 5 PubMed Johansen PB, Nowak J, Skjaerbaek C, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res 1999. PMID 10373343; doi:10.1054/ghir.1999.9998.
- 6 PubMed PubMed search: (ipamorelin[tiab]). 51 records at fetch. PMID ipamorelin.
- 7 ClinicalTrials.gov ClinicalTrials.gov registry search: ipamorelin. 3 registered studies at fetch.
- 8 PubMed Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs 1999. PMID 18031173; doi:10.2165/00063030-199912020-00007.