# Ipamorelin: Research Overview — Peptide Research Alliance > A structured literature summary of Ipamorelin, a selective GHS-R1a agonist and growth hormone secretagogue: mechanism, pharmacokinetics, human trial results, reported effects, safety cautions, and regulatory status. A synthetic pentapeptide agonist of the ghrelin receptor (GHS-R1a); notable for selective GH release without cortisol or prolactin elevation; never approved as a drug; its only human RCT did not meet its primary endpoint. ## The short version Ipamorelin is a synthetic five-amino-acid peptide that activates the ghrelin receptor — technically the growth hormone secretagogue receptor 1a (GHS-R1a) — on pituitary cells, triggering a pulse of growth hormone (GH) release [16][17]. Its defining pharmacological characteristic is selectivity: unlike related growth-hormone-releasing peptides such as GHRP-6 and GHRP-2, ipamorelin does not meaningfully raise ACTH (the stress hormone precursor), cortisol, or prolactin, even at doses far above its GH-release threshold. The important context: ipamorelin has **never been approved as a drug by the FDA or any other regulatory body**. It was investigated in one Phase 2 clinical trial for postoperative ileus and failed to meet its primary endpoint [15]. The FDA removed ipamorelin acetate from the Category 2 interim list for pharmacy compounding in 2024, following a nominator withdrawal, restricting compounding pharmacy access. It is prohibited in sport at all times under WADA category S2. This page describes the published evidence; it does not recommend use and lists no doses. ## What it is Ipamorelin is a synthetic pentapeptide with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 (where Aib is alpha-aminoisobutyric acid, and the D-amino acids at positions 3 and 4 provide protease resistance). It was derived from GHRP-1 by removal of a central dipeptide, producing a shorter and more selective agonist. Research designation: NNC 26-0161 (Novo Nordisk); also referred to as ipamorelin acetate or ipamorelin free base. It is a **research chemical**, not an approved medicine. It is not the same as the CJC-1295/ipamorelin combination product — that combination has its own research discussion separate from the individual agent studied in published ipamorelin trials. Ipamorelin is also distinct from CJC-1295, sermorelin (formerly Geref, approved and then withdrawn in 2008, now a 503A category-1 substance), and tesamorelin (FDA-approved for HIV-associated lipodystrophy only). ## How it works Ipamorelin selectively activates GHS-R1a receptors on pituitary somatotrophs, producing a discrete pulse of growth hormone release [16]. Population pharmacokinetic-pharmacodynamic modeling in healthy male volunteers showed dose-proportional kinetics, a terminal half-life of approximately 2 hours, and a GH response peaking roughly 40 minutes after dosing as a single pulse [16]. Bone growth was stimulated in adult female rats in a dose-dependent manner — longitudinal bone growth rate increased from 42 to 52 micrometers per day at the highest dose — without measurable changes in systemic IGF-1 or bone turnover markers, suggesting a partly local, GH-pulse-driven skeletal mechanism [17]. The ghrelin-receptor class also activates hypothalamic appetite circuits and has a direct insulinotropic effect on pancreatic islet cells, documented ex vivo. This dual GH-axis and metabolic influence means the compound's net effect on glucose metabolism is not straightforward. A 28-day chronic-dosing study in rats of a structurally distinct GHS-R1a agonist (not ipamorelin itself) found dose-dependent myocardial degeneration detectable by histopathology and elevated cardiac fatty-acid-binding protein — a class-level cardiovascular signal that frames why long-term systemic GHS-R1a agonism requires safety scrutiny [14]. ## What the research shows **Human PK/PD characterization (healthy male volunteers, 1999) [16]:** Population modeling across five 15-minute IV infusion doses (4.21–140.45 nmol/kg) showed linear, dose-proportional pharmacokinetics. Terminal half-life approximately 2 hours; steady-state volume of distribution 0.22 L/kg; GH response peaked ~40 minutes post-dose as a single discrete pulse. **Longitudinal bone growth in rats (1999) [17]:** Subcutaneous ipamorelin (18, 90, and 450 micrograms/day, divided three times daily for 15 days) dose-dependently increased longitudinal bone growth rate in adult female Sprague-Dawley rats without measurable changes in total IGF-1, IGFBPs, or bone turnover markers. **Phase 2 postoperative ileus trial (humans, n=114, 2014) [15]:** The only published Phase 2 RCT of ipamorelin (NCT00672074). Adults undergoing bowel resection received 0.03 mg/kg IV twice daily for up to 7 days. The primary endpoint — median time to first tolerated meal — was 25.3 hours with ipamorelin versus 32.6 hours with placebo (p = 0.15). **Primary endpoint not met.** Treatment-emergent adverse events occurred in 87.5% of the ipamorelin arm versus 94.8% of placebo; no ipamorelin-specific safety signal in this short perioperative window. **Class-level cardiovascular signal (rats, 2015) [14]:** A 28-day integrated preclinical safety study of a related GHS-R1a agonist found dose-dependent myocardial degeneration and necrosis in rats, detectable by histopathology and elevated cardiac fatty-acid-binding protein (FABP3); serum cardiac troponin was not elevated. Ipamorelin itself was not the compound tested; no equivalent long-duration cardiovascular study of ipamorelin exists. **Cisplatin-induced weight-loss inhibition in ferrets (2024) [13]:** Intraperitoneal ipamorelin (1–3 mg/kg) inhibited cisplatin-induced body-weight loss by approximately 24% on the last day of the delayed phase, but had no anti-emetic effect on acute or delayed emesis. The most recent published in-vivo ipamorelin study. ## Reported effects, cautions, and safety **Community-reported effects (anecdotal, not clinical evidence)** In research-use communities, the most consistently reported experience with ipamorelin is **deeper, more restorative sleep** — users describe falling asleep faster, sleeping more deeply, and waking more rested, with changes often appearing within one to two weeks of a pre-bedtime protocol. Vivid dreams are frequently mentioned in the early weeks. Other commonly reported benefits include faster physical recovery between training sessions, reduced muscle soreness, and — over weeks to months — a gradual shift toward a leaner body composition (confounded by concurrent diet and exercise in all accounts). Adverse effects most commonly noted include a transient facial flush and head-rush 5–15 minutes post-injection, occasionally tingling or numbness in the hands and feet, mild water retention and puffiness in the first two to four weeks, and increased hunger in the hours after injection — consistent with the ghrelin-receptor mechanism. Some users report that perceived effects diminish after three to four months of continuous use. All reports are anecdotal, unverified, and dose-unknown. **Safety cautions (citation-grounded)** - *Active or recent malignancy:* GH drives hepatic IGF-1 production, and IGF-1 is a well-characterized mitogen. Chronically raising GH-pulse amplitude may theoretically promote proliferative activity in pre-existing tumors [17]. No ipamorelin-specific carcinogenicity trial exists in humans. - *Diabetes or impaired glucose metabolism:* GH is a counter-regulatory hormone that reduces peripheral insulin sensitivity. Ipamorelin also has a direct insulinotropic effect on pancreatic islet cells documented ex vivo. This dual metabolic influence creates unpredictable net glycemic impact in people with pre-existing glucose dysregulation. - *Cardiovascular disease or significant edema:* A class-level signal from a 28-day study of a related GHS-R1a agonist showed dose-dependent myocardial degeneration in rats [14]. No equivalent long-duration safety study of ipamorelin itself exists; chronic cardiac risk in humans is uncharacterized. - *Appetite dysregulation or obesity-related conditions:* GHS-R1a agonists activate hypothalamic appetite circuits; GH-independent adiposity and leptin elevation have been documented in rodent studies. This orexigenic and potentially adipogenic signal is relevant for subjects managing caloric intake or adiposity. - *Unknown long-term human safety; no Phase 3 data:* The only controlled human ipamorelin data is one failed Phase 2 RCT (7-day perioperative window) [15] and an acute PK/PD study (n=8 per dose) [16]. No long-term human safety database exists. - *WADA prohibition:* Ipamorelin is prohibited in sport at all times under WADA category S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics). Detectable in urine. ## Where it fits in this research desk Ipamorelin represents the **growth hormone secretagogue** branch of research-peptide investigation — compounds that aim to stimulate GH release rather than supply GH directly. Its place on this desk is anchored by its pharmacological selectivity profile, which is its most rigorously characterized feature, and by its cautionary story: despite years of preclinical work and widespread promotion, its only prospective controlled human trial failed its primary endpoint. Marketing of ipamorelin for anti-aging, fat loss, and muscle building substantially outpaces the controlled human evidence. For researchers interested in adjacent compounds: [BPC-157](/bpc-157) approaches tissue recovery from the cytoprotection and angiogenesis side; [NAD+](/nad) engages the metabolic and longevity-signaling layer through a different, coenzyme-level mechanism. [Compare all five compounds](/compare) for a side-by-side view. --- An independent literature digest of peer-reviewed research — definitional, cited, and free of products, prescriptions, and dosing recommendations.