Two receptors, one pituitary cell
Table 1 at the top answers the comparison with published numbers only; the rest of the page says where each cell comes from. The diagram shows the one difference that decides the rest: which receptor each peptide presses.
- GHRH receptorAmount
- Ghrelin receptorTrigger
- Both at onceBigger burst
| Study | What the authors wrote |
|---|---|
| Corpas et al., 1992 J Clin Endocrinol Metab | Short term sc administration of GHRH to healthy old men reverses age-related decreases in GH and IGF-I. |
| Raun et al., 1998 European Journal of Endocrinology | Ipamorelin is the first GHRP-receptor agonist with a selectivity for GH release similar to that displayed by GHRH. |
| Ionescu and Frohman, 2006 J Clin Endocrinol Metab | CJC-1295 increased trough and mean GH secretion and IGF-I production with preserved GH pulsatility. |
One family, one stranger
Sermorelin and CJC-1295 are relatives. Both are the N-terminal 29 residues of human growth-hormone-releasing hormone, the fragment identified as fully active when the hormone was first characterised from a pancreatic tumour in 1982 [1]. Sermorelin is that fragment as found, amidated; it was reviewed as a licensed product in 1999 and used both as a stimulation test for growth hormone deficiency and in prepubertal children with idiopathic GH deficiency [2]. CJC-1295 is the fragment with four residues swapped for stability and a maleimide tail that binds serum albumin, which is the whole reason its numbers differ (the chemistry is in Mod GRF 1-29 and DAC versus no DAC).
Ipamorelin is not a relative. It is a five-residue synthetic peptide from an entirely different programme, at Novo Nordisk, built to mimic the GHRPs and to act on what is now called the ghrelin receptor, GHS-R1a, without the cortisol and prolactin release of its predecessors [7]. It shares nothing with the other two except the cell it acts on: the pituitary somatotroph carries both receptors, and a GHRH signal and a ghrelin signal arriving together release more GH than either alone. That synergy was shown in men by Bowers in 1990, with GHRH(1-44) and GHRP-6 [9]; it is the reason CJC-1295 and ipamorelin are sold as a pair and sermorelin usually is not.
Minutes, hours, days
The largest single difference among the three is how long each lasts. Sermorelin is cleared in minutes; the practical evidence is that Corpas and colleagues, at the National Institute on Aging, had to give GHRH(1-29) repeatedly each day for 14 days to raise 24-hour GH and IGF-1 in ten men aged 68, and only the higher of two study arms did so.
In the higher arm the older men's GH and IGF-1 no longer differed from those of nine men aged 26, and fasting glucose, blood pressure and blood chemistry were unchanged [3]. Ipamorelin lasts about two hours after an intravenous infusion and produces one GH episode that peaks at 40 minutes [8]. CJC-1295 with its albumin tail lasts 5.8 to 8.1 days, and in the trial a single administration held GH 2 to 10-fold above baseline for 6 days or more and IGF-1 1.5 to 3-fold for 9 to 11 days [5].
The consequence for the GH rhythm is the second difference. Sermorelin and ipamorelin each produce a pulse and leave. CJC-1295 raised the trough between pulses 7.5-fold without changing the number or size of the pulses, so mean GH rose 46 % and IGF-1 45 % one week after a single administration [6]. Whether a raised trough or a bigger pulse is the better way to raise IGF-1 is a physiological argument, made for GHRH analogues in general by Walker in 2006 on the ground that they preserve pituitary feedback where recombinant GH does not [4]; the argument applies to all three molecules equally, since all three work through the pituitary.
GH secretion was increased after CJC-1295 administration with preserved pulsatility.
Figure 5
Half-life in humans (log scale)
- Sermorelin, GHRH(1-29)minutes
- Ipamorelin2 hours
- CJC-1295 with DAC5.8 to 8.1 days
Who has human data, and how much
| Molecule | Human studies | Largest | Outcomes measured |
|---|---|---|---|
| Sermorelin | diagnostic and paediatric treatment programme; older men [2] [3] | treatment series to 36 months in children | GH response, height velocity, IGF-1, tolerability |
| CJC-1295 | 2 JCEM trials [5] [6] | healthy adults, 28 and 49 days | GH, IGF-1, half-life, pulsatility, tolerability |
| Ipamorelin | 1 PK study, 2 phase 2 ileus trials [8] | 320 participants (results unpublished) | kinetics, GH episode, primary clinical endpoint |
| CJC-1295 + ipamorelin | none | none | none |
The table is the part of the comparison most pages leave out. Sermorelin was a licensed medicine with a paediatric programme long enough to follow height velocity for 36 months [2]. CJC-1295 has two well-designed but small trials in healthy adults. Ipamorelin's largest trial had nothing to do with growth hormone. And the pair has no trial at all. The record of CJC-1295 alone is in CJC-1295 peptide.
Regulatory status
Sermorelin is the only one of the three that has ever been an approved drug, and the product reviewed in 1999 is no longer marketed. CJC-1295's phase 2 trial was terminated in 2006 and ipamorelin's ileus programme stopped in 2014, so neither reached approval anywhere. All three are prohibited in sport: the WADA list names CJC-1295, sermorelin and tesamorelin among GHRH analogues and ipamorelin among growth hormone secretagogues, class S2 [10]. The molecule that did complete a programme, tesamorelin, is the subject of tesamorelin ipamorelin vs CJC-1295 ipamorelin. Sermorelin itself now circulates as a research reagent, for example the 5 mg sermorelin research vial from OXpeptides.
What the comparison cannot settle
It cannot say which is "better", because no study has compared them. It can say that sermorelin is the best-documented, that CJC-1295 is the longest-acting and the only one shown to raise trough GH without flattening pulses, that ipamorelin is the most selective GHRP by the criteria its designers set, and that combining a GHRH analogue with a GHRP has a 36-year-old proof of principle in humans with different molecules. Anyone who tells you more than that is not reading the same literature.
