The map
Four compounds, three targets, one shared output
Mechanism, duration and evidence maturity are three different axes, and a compound can sit high on one and low on the others. Collapsing them is how a category ends up describing four unlike things as interchangeable.
Start here
Comparing these four compounds usually goes wrong in the same way. A list is drawn up, everything gets a row, and the rows are read as if they were versions of one product — mild, strong, short, long.
They are not versions of one product. Two of them push the same button on the pituitary and differ almost entirely in how long they last. A third pushes a completely different button on the same cell. The fourth works inside muscle cells and never touches the pituitary at all.
So this page separates the comparison into three questions instead of one. Where does each compound act? How long does its effect last? And how good is the evidence that it does anything useful in people? A compound can score well on the first two and badly on the third, and one on this map does exactly that. None of the tables below contains a quantity anyone could use as a dose, because that is not what this site is for.
The receptor map
Where each compound actually acts, and what the axis does in response.
| Compound | Molecular target | GH pulsatility | IGF-1 |
|---|---|---|---|
| CJC-1295 | GHRH receptor (GHRHR), on the anterior-pituitary somatotroph | Preserved: frequency and magnitude unaltered under continuous stimulation [5] | Raised, and for days after a single administration [4] |
| Ipamorelin | GHS-R1a, the ghrelin receptor, on the same somatotroph | One discrete pulse per administration [11] | No change in total IGF-1 in the rat growth study [12] |
| Sermorelin | GHRH receptor (GHRHR), on the anterior-pituitary somatotroph | Preserved; somatostatin and IGF-1 feedback stay intact | Raised without excessive generation in the pediatric trial [16] |
| MOTS-c | Folate cycle, AMPK, NRF2-linked genes and casein kinase 2, in skeletal muscle [17] | Not applicable | Not applicable |
The intracellular routes differ as much as the targets do. Both GHRH-receptor agonists work through adenylate cyclase, cAMP and PKA — sermorelin as the unmodified native signal [1], CJC-1295 as the same signal conjugated to albumin in its DAC form [7]. Ipamorelin reaches the same secretory machinery by a distinct route that is complementary to GHRH rather than parallel to it, and GHS-R1a is expressed well beyond the pituitary: on enteric and vagal neurons, on pancreatic islets, and in hypothalamic appetite circuitry. MOTS-c has no receptor on the somatotroph at all; its signalling is intracellular and metabolic, extending to the nucleus under stress [21].
Read down the target column and the category dissolves. Two GHRHR agonists, one GHS-R1a agonist, and one compound whose targets are enzymes and transcription factors inside a muscle cell.
Duration is a separate axis from mechanism
Two compounds can share a receptor and behave completely differently in time, and that is the sharpest distinction on this map.
CJC-1295 with DAC has an estimated half-life of 5.8 to 8.1 days; single administrations produced 2- to 10-fold increases in mean plasma GH for six days or more and 1.5- to 3-fold increases in IGF-1 for nine to eleven days, with IGF-1 still above baseline as far out as 28 days after repeated administration [4]. Ipamorelin's terminal half-life is approximately 2 hours, with the GH response peaking around 40 minutes as a single discrete pulse [11]. Sermorelin is the native fragment with native clearance, which is why the compound is studied as an intermittent signal. CJC-1295 without DAC — Modified GRF (1-29) — keeps the protease-resistant substitutions but not the albumin handle, and is short-acting; product listings that treat it and the DAC form as one compound make every duration figure above unattributable.
One finding keeps the duration axis honest. A long plasma residence is not a long biological effect: in GHRH-knockout mice, daily administration of CJC-1295 fully normalised body weight and length, while 48- and 72-hour intervals were progressively less effective [6]. Days of measurable peptide did not equal days of equivalent axis output. And in the opposite direction, continuous rather than intermittent GHRH(1-29) exposure in children caused the growth-hormone response to fade over months, with one child's secretion fully suppressed. The axis defends its own rhythm at both ends.
The evidence-maturity map
Mechanism and evidence do not rank the same way, and this is the table most often left out of a comparison.
| Compound | Strongest human evidence | What it showed | Regulatory position |
|---|---|---|---|
| CJC-1295 | Early PK/PD studies in healthy volunteers [4][5] | Duration and magnitude of GH and IGF-1 elevation, with pulsatility preserved | No approval anywhere; not recommended for the Section 503A bulks list; research chemical |
| Ipamorelin | A Phase 2 randomised controlled trial in 114 adults after bowel resection, plus a single-dose PK/PD study [10][11] | Primary endpoint missed: 25.3 h against 32.6 h to first tolerated meal, p = 0.15 [10] | Removed from Category 2 of the interim 503A list in 2024 and reviewed at the October 2024 advisory committee; never approved |
| Sermorelin | A multicentre efficacy trial in prepubertal GH-deficient children [16]; separately, class-level adult data from a 152-participant tesamorelin (Egrifta) trial [13] | Height velocity rose from about 4.1 to roughly 7-8 cm per year without excessive IGF-1 [16] | Held a US approval for pediatric GH deficiency, withdrawn in 2008 for commercial reasons; now Category 1 under the interim 503A policy |
| MOTS-c | An observational cohort of 94 chronic haemodialysis patients, measuring the body's own circulating peptide [18] | Endogenous MOTS-c independently associated with mortality and cardiovascular events; improved risk-model discrimination | Not approved for any use; research chemical only; no validated human pharmacokinetics |
The two tables rank the four compounds in almost opposite orders. CJC-1295 has the cleanest human axis pharmacology and no outcome trial. Ipamorelin has the only completed randomised controlled trial on the desk, and it missed. Sermorelin has the only positive controlled efficacy result, in children, for an indication almost nobody buys it for. MOTS-c has the most interesting mechanism and no interventional human data whatsoever.
Where the marketing treats them as interchangeable
Three specific collapses, each of which the map above resolves.
"GH peptides" as a single class. The label holds for three of the four and fails completely for MOTS-c, whose targets are the folate cycle, AMPK, NRF2-linked genes and CK2 [17][19][21] — none of them on a pituitary cell. Selling it beside the secretagogues is a shelving decision.
"CJC-1295" as a single compound. DAC and no-DAC share a scaffold and not a pharmacokinetic profile [4][7]. Any duration, exposure or effect claim that does not name the form is uninterpretable.
The GHRH-analog-plus-ipamorelin pairing as a tested protocol. The mechanistic rationale is real: two separate receptors on the same cell, additive rather than redundant. The evidence is two single-agent literatures placed side by side. No trial of the combination against any outcome exists, and the map should show that as a gap rather than a bridge.
One more distinction runs underneath all three. Sermorelin's regulatory history is an approval that was commercially withdrawn; ipamorelin's is a development programme that completed and missed [10]; CJC-1295's is a programme that was discontinued; MOTS-c's is a compound that has never entered human interventional testing. Four different kinds of "not approved", routinely reported as one.