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 patients (results unpublished) | kinetics, GH episode, time to first meal, adverse events |
| 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; its most frequent adverse events were transient facial flushing and local pain [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. What the trials recorded as adverse events is in CJC-1295 side effects.
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 in HIV-associated visceral fat 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. The public price of the licensed hormone, somatropin, in France is tabulated in French in prix de l'hormone de croissance. Sermorelin itself now circulates as a research reagent, for example the 5 mg sermorelin research vial from OXpeptides, the shop run by the publisher of this site.
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.
