GROWTH HORMONE AXIS / COMPARE
Three Peptides, Side by Side
Where the three GH-axis peptides converge, where they diverge by mechanism, and — most usefully — how thin or thick the human evidence actually is behind each.
The short version
This page lines up ipamorelin, CJC-1295, and sermorelin on six dimensions that matter when reading research-peptide literature: peptide class and mechanism, most-studied contexts, evidence base, administration routes, regulatory/WADA status, and the single defining caution for each. The headline is direct. All three raise growth hormone through the pituitary, but by different receptors and with strikingly different evidence profiles: sermorelin has the only real controlled pediatric efficacy data plus a stable compounding status; ipamorelin has one failed Phase 2 human trial and detailed human PK data; CJC-1295 has two pharmacology studies and no efficacy trial. None is an approved medicine for general adult use, and none is presented here with a human dose.
The comparison matrix
| Dimension | Ipamorelin | CJC-1295 | Sermorelin |
|---|---|---|---|
| Peptide class | Synthetic pentapeptide; selective GHS-R1a (ghrelin receptor) agonist | Tetrasubstituted GHRH analog; DAC variant covalently binds albumin for multi-day half-life | 29-aa N-terminal GHRH fragment; shortest fully bioactive GHRH analog |
| Most-studied in | GH-pulse selectivity (cortisol/prolactin sparing); postoperative ileus (human trial) | GH/IGF-1 elevation pharmacokinetics; serum proteome shifts; anti-doping identification | Pediatric GH deficiency (approved indication); GH-axis and cognition (related class) |
| Evidence base (model) | Rat/swine pharmacology; n=8 human PK; n=114 Phase 2 RCT (primary endpoint not met) [3][4][6] | n=11 human proteomics; two healthy-volunteer PK studies (no efficacy trial) [10][11][12] | Pediatric multicenter RCT (approved); 1 adult cognition RCT (related compound) [13][16] |
| Administration studied | IV (human PK + Phase 2 trial); subcutaneous (animal); SC community use uncharacterized in humans [3][4] | Subcutaneous (human PK studies); IV not studied in humans [11][12] | Subcutaneous (approved clinical use; pediatric trial) [16] |
| Regulatory / WADA status | Not approved; removed from 503A Category 2 (2024); WADA S2 prohibited | Not approved; not on 503A bulks list; WADA S2 prohibited | Previously FDA-approved (NDA 020443; pediatric GH deficiency); commercially withdrawn 2008; Category 1 503A bulk substance; WADA S2 prohibited |
| Key caution | Only Phase 2 human trial missed primary endpoint; class-level chronic cardiotoxicity signal [2][3] | No completed efficacy trial; DAC vs no-DAC distinction routinely collapsed; development program discontinued [11] | Anti-aging use not evidence-supported; approval history routinely misstated in both directions [14][15] |
Peptide class
Ipamorelin and the two GHRH analogs activate different receptors on the same pituitary cell. Ipamorelin is a GHS-R1a agonist — it mimics ghrelin, the hunger/GH-secretagogue hormone — and it triggers a discrete GH pulse without cortisol or prolactin elevation [6]. CJC-1295 and sermorelin both act on the GHRH receptor, but their pharmacokinetics are very different: sermorelin behaves close to the native 29-residue fragment (short-acting, physiologic pulse), while CJC-1295 with its albumin-binding DAC moiety produces sustained days-long GH and IGF-1 elevation [8][11]. The two receptor classes are sometimes combined because they are complementary — but their combination as a "stack" has no controlled human trial behind it.
Most-studied in
Each peptide has a different home territory in the literature. Ipamorelin's published research centers on its founding selectivity characterization (cortisol and prolactin sparing), bone growth in rats, human PK/PD, and the single perioperative ileus trial [3][5][6]. CJC-1295's published record is narrower: two healthy-volunteer PK studies, a serum proteomics observation, and anti-doping identification work [9][10][11][12]. Sermorelin's controlled efficacy data come from pediatric GH deficiency — the approved indication — and a class-level RCT using a related compound for cognition in older adults [13][16].
Evidence base (model)
This dimension separates the three most clearly. Sermorelin has the strongest controlled efficacy record, but it is in pediatric patients with diagnosed GH deficiency — the adult anti-aging use case lacks a comparable RCT [16]. Ipamorelin has the only human Phase 2 efficacy trial in this group, which enrolled 114 adults and did not meet its primary endpoint [3]. CJC-1295 has the richest pharmacokinetic demonstration — sustained, days-long GH and IGF-1 elevation confirmed in humans — paired with zero completed efficacy trials [11][12]. All three lack long-term human safety data.
Administration studied
Ipamorelin was given intravenously in both human studies (PK/PD and Phase 2 trial); subcutaneous use dominates community practice but has no published human PK characterization [3][4]. CJC-1295 human studies used subcutaneous injection [11][12]. Sermorelin's approved use and its supporting pediatric RCT used subcutaneous injection, consistent with the standard approach to GHRH analogs [16]. Oral, sublingual, and intranasal routes for any GHRH analog are not supported by the pharmacokinetics.
Regulatory / WADA status
None of the three is approved for general adult use. Sermorelin occupies the strongest regulatory position: it has a withdrawn FDA approval (not a revoked or safety-based withdrawal), and it holds Category 1 status under FDA's interim 503A compounding policy — meaning compounding pharmacies can prepare it without current enforcement concern [15]. Ipamorelin and CJC-1295 are in a different position: ipamorelin was removed from the 503A Category 2 list in 2024, and CJC-1295 is not on the approved compounding bulks list. All three are prohibited at all times in sport under WADA S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics).
Key caution
Each compound carries a defining caveat that should travel with any discussion of it. For ipamorelin, it is that the only Phase 2 human efficacy trial missed its primary endpoint, and that a 28-day preclinical study of a related GHS-R1a agonist found dose-dependent myocardial degeneration in rats — a class-level cardiac signal without a human parallel [2][3]. For CJC-1295, it is the combination of zero efficacy trials and a routinely misread naming convention: CJC-1295 DAC and Modified GRF 1-29 are pharmacokinetically distinct but marketed interchangeably [11]. For sermorelin, it is that the evidence supporting adult anti-aging use does not exist in the peer-reviewed literature, and that its approval history is misread in both directions — neither condemned nor as broadly validated as some sources imply [14][15]. Reading all three together, the lesson is consistent: compelling receptor pharmacology, real GH/IGF-1 pharmacodynamics in humans, and thin-to-absent controlled efficacy data in the populations most interested in these compounds.