What is ipamorelin used for?

What it is being studied for

• Gut shutdown after bowel surgery (postoperative ileus): a phase 2 human randomized trial in 114 analysed patients that missed its primary endpoint — median time to the first tolerated solid meal was 25.3 vs 32.6 hours with placebo (p=0.15), with no significant differences in secondary endpoints [1].
• Postoperative ileus, second trial: a registered human randomized trial (NCT01280344, 320 enrolled) is listed as completed, with no results posted and no publication found [2].
• Growth hormone release in healthy men: a small human dose-finding study (8 men per dose, intravenous infusion) reported a rise in growth hormone at every dose, as a single peak about 40 minutes in, and a half-life of about 2 hours; the abstract does not describe a comparator group [3].
• Selective hormone release: in a laboratory and animal study (rat pituitary cells, rats, pigs), growth hormone rose without a rise in the stress hormones ACTH or cortisol, even at over 200 times the dose giving a half-maximal growth hormone response [4].
• Bone growth: an animal study in adult female rats reported bone growth rising from 42 to 52 micrometres a day and dose-dependent weight gain over 15 days, with IGF-I unchanged [5].
• Steroid-induced bone and muscle loss: an animal study in rats given methylprednisolone for 3 months reported 4-fold higher bone formation on the bone surface and stronger muscle contraction than with the steroid alone [6].
• Postoperative ileus in rodents: an animal study reported a shorter time to first bowel movement after one dose, and more fecal output and food intake with repeated doses [7].
• Chemotherapy-related weight loss: an animal study in ferrets given cisplatin reported no change in vomiting but less weight loss and less drop in feeding (abstract read) [8].
• No human trial of growth-hormone-related outcomes beyond the 1999 volunteer study was found; the bone, muscle and weight effects above have been shown only in animals.

How it works

1. It is a five-amino-acid peptide made by removing the middle two amino acids of an older growth-hormone-releasing peptide, GHRP-1; laboratory receptor tests placed its action at a GHRP-type receptor, not the receptor for the body’s own growth-hormone-releasing hormone [4].
2. Later studies describe it as an activator of the ghrelin receptor (GHS-R1a), the same receptor the hunger hormone ghrelin uses [7][8].
3. In healthy men given an intravenous infusion, growth hormone rose as a single peak about 40 minutes in, and ipamorelin itself had a half-life of about 2 hours [3].
4. In rats, it was cleared from the blood 5 times more slowly than GHRP-6 and left the body mainly unchanged in urine [9].
5. What sets it apart from its closest relatives, GHRP-6 and GHRP-2: in pigs, those two raised the stress hormones ACTH and cortisol along with growth hormone, while ipamorelin raised growth hormone without a significant rise in either — the basis of the 1998 paper’s description of it as the first selective growth hormone secretagogue [4].

Adverse events reported

• Phase 2 ileus trial: treatment-emergent adverse events in 87.5% of the ipamorelin group vs 94.8% of the placebo group; the authors described it as well tolerated for up to 7 days. The abstract does not list the event types [1].
• Healthy-volunteer study: the abstract reports no safety data [3].
• Second ileus trial (NCT01280344): no results posted, so no adverse-event data are available [2].

Forms

Intravenous infusion is the only form studied in humans, in the volunteer study and the ileus trial [3][1]. Subcutaneous injection appears only in rat studies; no human trial of it was found [5][6]. Nasal delivery reached about 20% bioavailability in rats [9], and one human volunteer was given nasal ipamorelin in a doping-control urine study with no efficacy data [10]. No oral ipamorelin study was found; NN703, an orally active secretagogue derived from it, is a different compound [11].

How injections, nasal sprays and oral forms of peptides compare across the field: Peptide pills vs nasal sprays vs injections.