Ipamorelin
Also known as: Ipamorelin acetate, NNC 26-0161
Evidence: Preclinical
Overview
Pentapeptide ghrelin-receptor agonist that released GH without raising ACTH or cortisol in swine (Raun 1998); human data are a PK study (n=40) and one negative phase 2 trial in postoperative ileus (n=114).
Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH2, Novo Nordisk NNC 26-0161) was derived from GHRP-1. In rat pituitary cells and anesthetized rats it released GH with potency similar to GHRP-6; in swine it did not raise ACTH or cortisol even at 200 times the GH ED50, unlike GHRP-2 and GHRP-6 (Raun 1998). In rats it increased longitudinal bone growth and body weight (Johansen 1999), bone mineral content (Svensson 2000) and countered glucocorticoid-induced loss of bone formation and muscle strength (Andersen 2001). Human data: a 15-minute IV infusion study in 40 volunteers gave dose-proportional PK, a 2 h half-life and one GH peak at 40 min (Gobburu 1999); a phase 2 randomized trial of 0.03 mg/kg IV twice daily for postoperative ileus found no efficacy difference from placebo (Beck 2014, n=114). No human body-composition trial has been published.
Benefits
GH release without ACTH or cortisol rise (swine), longitudinal bone growth and bone mineral content (rat), counteracted glucocorticoid bone and muscle loss (rat), dose-proportional GH release in human volunteers (PK study)
Dosing reference
- Research dose
- Human data: 4-140 nmol/kg IV over 15 min (PK study) and 0.03 mg/kg IV 2x daily (ileus trial); research-community range 100-300 mcg SC 1-3x daily
- Range
- 100 to 300 mcg, 2-3x daily
- Reconstitution
- 2 mL bacteriostatic water
- Common vial sizes
- 2 mg, 5 mg
Subcutaneous in research use; human studies used IV infusion. GH peaks about 40 min after IV dosing and returns to baseline within hours (Gobburu 1999). In rats given ipamorelin three times daily for 15 days, the pituitary GH response to a test dose was marginally reduced (Johansen 1999). Rat ileus work used 0.1-1 mg/kg IV four times daily (Venkova 2009).
Mechanism
Ipamorelin is an agonist at the ghrelin receptor GHS-R1a and releases GH through a GHRP-like receptor pathway distinct from GHRH, shown with GHRP and GHRH antagonists in rat pituitary cells (Raun 1998). Its distinguishing property is selectivity: in swine it released GH with potency similar to GHRP-6 but did not raise ACTH, cortisol, FSH, LH, prolactin or TSH (Raun 1998). GH release in humans is dose-dependent, with half-maximal stimulation at a plasma concentration of 214 nmol/L (Gobburu 1999). Like other ghrelin mimetics it accelerates gut transit in rats, the basis of the postoperative-ileus trial (Venkova 2009).
Evidence
Preclinical: animal or in vitro data only
- Released GH with GHRP-6-like potency but without ACTH or cortisol rise in swine; no effect on prolactin (Raun et al., 1998)
- Dose-proportional PK, 2 h terminal half-life and a single GH peak at 40 min after IV infusion in 40 healthy men (Gobburu et al., 1999)
- Increased longitudinal bone growth rate and body weight in rats at 18-450 mcg/day SC (Johansen et al., 1999)
- Countered glucocorticoid-induced loss of bone formation and muscle strength in adult rats (Andersen et al., 2001)
- Phase 2 RCT in postoperative ileus (0.03 mg/kg IV twice daily, n=114): well tolerated, no efficacy difference from placebo (Beck et al., 2014)
- Human-trial status: one PK study and one negative phase 2 RCT; no body-composition trial; not approved anywhere
References
- Ipamorelin, the first selective growth hormone secretagogue. Raun K, Hansen BS, Johansen NL, et al., European Journal of Endocrinology, 1998
- Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Gobburu JV, Agerso H, Jusko WJ, Ynddal L, Pharmaceutical Research, 1999
- Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Johansen PB, Nowak J, Skjaerbaek C, et al., Growth Hormone & IGF Research, 1999
- The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. Svensson J, Lall S, Dickson SL, et al., Journal of Endocrinology, 2000
- The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Andersen NB, Malmlof K, Johansen PB, Andreassen TT, Ortoft G, Oxlund H, Growth Hormone & IGF Research, 2001
- Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B, Journal of Pharmacology and Experimental Therapeutics, 2009
- Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group, International Journal of Colorectal Disease, 2014
Side effects
In the ileus RCT, treatment-emergent adverse events were 87.5% with ipamorelin vs 94.8% with placebo in post-surgical patients, with no safety signal (Beck 2014). Injection-site reactions, a transient head rush, mild water retention, and with sustained GH elevation joint aches and reduced insulin sensitivity are commonly reported (anecdotal). Regulatory: ipamorelin acetate is on FDA's 503B category 2 (significant safety risks) table, added 2023-09-29, and in the 503A withdrawn-nomination table, page content as of 2026-04-22: https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
Storage
- Storage
- Refrigerated (2-8°C)
- Lyophilized
- 24+ months at room temperature
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- ~2 h terminal (human, IV infusion; Gobburu 1999)
- Molecular weight
- 711.86 Da
- Sequence
- [Aib]H[D-2-Nal][D-F]K[NH2]