Research in plain language

Ipamorelin

What it is

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) that selectively activates the ghrelin receptor (GHS-R1a) to trigger pulsatile growth hormone (GH) release from the pituitary. It is mainly studied as a selective GH secretagogue and was tested in humans as a ghrelin mimetic to speed gut recovery after bowel surgery.

How studies used it

Model: Rat (anaesthetized) and conscious swine; also rat pituitary cells in vitro
Studied for: GH-release pharmacology and receptor selectivity (the founding characterization study)
Dose: Rat GH-release ED50 about 80 nmol/kg (roughly 0.057 mg/kg at MW 711.9). Swine GH-release ED50 about 2.3 nmol/kg (roughly 0.0016 mg/kg, i.e. about 1.6 ug/kg). In vitro EC50 1.3 nmol/L
Dosing: Single intravenous bolus doses across a dose-response range
Route: Intravenous (in vivo); cell culture (in vitro)
Duration: Acute single-dose pharmacology

Effects measured: Dose-dependent GH release. In rats maximal GH about 1545 ng/mL; in swine maximal GH about 65 ng/mL. In vitro maximal GH release about 85 percent of reference. Highly selective: even at doses over 200-fold the GH ED50, ipamorelin did not raise ACTH or cortisol above GHRH-stimulated levels, and did not change FSH, LH, prolactin or TSH, unlike GHRP-6 and GHRP-2

Side effects: No adverse events reported in this study (selectivity was the main finding: no ACTH/cortisol/prolactin elevation)

Sources: Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561.

Model: Human, adults undergoing open or laparoscopic small/large bowel resection
Studied for: Postoperative ileus (Phase 2 proof-of-concept randomized, double-blind, placebo-controlled trial); LARGELY NEGATIVE
Dose: 0.03 mg/kg per dose (already weight-based; mean/median patient body weight was not reported in the abstract, so no kg figure is needed beyond the per-kg dose itself)
Dosing: Twice daily
Route: Intravenous infusion
Duration: Postoperative day 1 through day 7 or hospital discharge

Effects measured: Did NOT meet its primary endpoint. Median time from first dose to tolerating a standardized solid meal was 25.3 h with ipamorelin vs 32.6 h with placebo, p = 0.15 (not statistically significant). 117 enrolled, 114 in safety and modified intent-to-treat analyses

Side effects: Treatment-emergent adverse events in 87.5 percent of ipamorelin patients vs 94.8 percent of placebo (no excess vs placebo); nausea and vomiting were among the events noted

Sources: Beck DE, Sweeney WB, McCarter MD. 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.

Model: Rat, male Sprague-Dawley (preclinical postoperative ileus model)
Studied for: Postoperative ileus (the animal model that supported the later human trial)
Dose: 0.01 to 1 mg/kg (range tested); effects at 0.1 to 1 mg/kg
Dosing: Single IV bolus, or repetitive dosing of four doses daily at 3-hour intervals over 2 days
Route: Intravenous bolus
Duration: Single dose, or 2 days for repetitive dosing (48 h monitoring)

Effects measured: A single 1 mg/kg dose shortened the time to first bowel movement after laparotomy with intestinal manipulation, without changing total stool output. Repetitive dosing (0.1 to 1 mg/kg) significantly increased cumulative fecal pellet output, food intake, and body weight gain

Side effects: No adverse events reported in this study

Sources: Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009;329(3):1110-1116.

Model: Rat, female Wistar, 8 months old
Studied for: Glucocorticoid-induced loss of bone formation (osteoporosis model)
Dose: 100 ug/kg (0.1 mg/kg) per dose
Dosing: Three times daily
Route: Subcutaneous injection
Duration: 3 months

Effects measured: Co-treatment with methylprednisolone (9 mg/kg/day): adding ipamorelin increased the periosteal bone formation rate about four-fold versus glucocorticoid alone, and improved maximum tetanic tension of calf muscles. Groups of 8 rats each (control, glucocorticoid, ipamorelin, combination)

Side effects: No adverse events reported in this study

Sources: Andersen NB, Malmlof K, Johansen PB, Andreassen TT, Ortoft G, Oxlund H. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res. 2001;11(5):266-272.

Model: Rat, female Wistar
Studied for: Whether glucocorticoid (methylprednisolone) blunts ipamorelin-driven GH release and catabolism
Dose: 0.4 mg/kg/day and 1.6 mg/kg/day
Dosing: Divided into four IV injections per day
Route: Intravenous
Duration: 8 to 10 days

Effects measured: Methylprednisolone (5.0 mg/kg) did not blunt the acute plasma GH response to ipamorelin or GHRH. When given with methylprednisolone, ipamorelin significantly reduced glucocorticoid-induced body weight loss and raised IGF-I levels

Side effects: No adverse events reported in this study

Sources: Malmlof K, Johansen PB, Haahr PM, Wilken M, Oxlund H. Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats. Growth Horm IGF Res. 1999;9(6):445-450.

How solid the evidence is

Mixed and skewed toward animal data. The mechanistic and dose-response evidence is solid but mostly preclinical: the founding pharmacology (Raun 1998, PMID 9849822) is a clean rat-plus-swine study with per-kg ED50 values and clear selectivity (no ACTH/cortisol/prolactin rise), but it is acute single-dose and over 25 years old. The bone (PMID 11735244), catabolism/GH (PMID 10629165), and chronic somatotroph studies are all small single-lab rat studies (groups of about 8), several from the same Danish group (the developer Novo Nordisk lineage), so they share a sponsor-adjacent perspective and are not independently replicated at scale. The most important human data point is NEGATIVE: the Phase 2 postoperative ileus RCT (Beck 2014, PMID 25331030, 117 patients) did NOT meet its primary endpoint (time to tolerate a solid meal 25.3 h vs 32.6 h, p = 0.15). Safety in that human trial was reassuring (adverse events no higher than placebo), but efficacy was not demonstrated. There are NO published long-term human safety or efficacy trials for the muscle, bone, anti-aging, or body-composition uses ipamorelin is popularly marketed for; that marketing is an extrapolation from short rodent studies plus acute human GH-secretion pharmacology, not from controlled human outcome trials. Doses: the human trial dose (0.03 mg/kg) is inherently per-kg, and patient body weight was not reported. The rat/swine ED50 values were published in nmol/kg and converted here to mg/kg using ipamorelin MW 711.9; treat the converted figures as approximate.

Sources

Study data, research use only. No established human dosing protocol.