Growth-Hormone-Axis Compounds Compared
Sermorelin vs Ipamorelin: Two Receptors, One Axis, One Regulatory History
These two are listed side by side as though they were siblings. They are not. Sermorelin copies the first 29 residues of a human hormone and acts at that hormone’s own receptor; ipamorelin is a designed pentapeptide acting at the receptor ghrelin binds. Research-use reference only: no dosing, route, frequency or medical advice.
The short answer
They drive the same downstream axis through two different receptors, and only one has a regulatory history. Sermorelin is GHRH(1-29)-amide acting at the GHRH receptor, and it was an FDA-approved drug — GEREF — under two separate new drug applications before its sponsor discontinued it. Ipamorelin is a five-residue synthetic peptide acting at GHS-R1a, never approved by any regulator, its development stopped at Phase 2. Nearly every practical difference follows: one molecule is a hormone fragment vulnerable to a specific plasma enzyme and the other is engineered not to be, and one has an FDA-reviewed record behind it while the other has a single published trial that missed its endpoint.
Two receptors, one axis
Sermorelin engages the GHRH receptor because it is the active front of that receptor’s natural ligand. UniProt P01286 records human somatoliberin, whose mature hormone begins at residue 32 of the precursor; sermorelin reproduces its first 29 residues with an amidated C-terminus — not an analog in the loose sense, but the hormone’s own N-terminal fragment.
Ipamorelin engages a different receptor, and that history is routinely garbled. Raun et al. characterised it in 1998 (PMID 9849822) as a growth-hormone-releasing-peptide receptor agonist. The receptor had been cloned by then (Howard et al., 1996, PMID 8688086) but was still an orphan, and its endogenous ligand was not identified until Kojima et al. described ghrelin the following year (PMID 10604470). “Ipamorelin is a ghrelin receptor agonist” is therefore correct but retrospective: it was characterised before anyone knew what that receptor was for.
“Selective” does not mean receptor exclusivity either. In Raun’s work it meant selectivity of output: ipamorelin did not raise ACTH or cortisol above what GHRH stimulation produced, even at more than 200-fold its GH ED50, whereas GHRP-6 and GHRP-2 did. That is a real finding, and it was obtained in conscious swine — the paper’s other preparations were primary rat pituitary cells and pentobarbital-anaesthetised rats. None of it was done in people.
A related gap is worth naming precisely, because it is the sort of thing usually papered over with a borrowed number. The figure Raun reports for ipamorelin is a functional potency — GH release from primary rat pituitary cells with an EC50 of 1.3 ± 0.4 nmol/L — not a receptor binding constant. Reading the indexed abstracts that connect ipamorelin to GHS-R1a, we did not find a published Ki or IC50 for ipamorelin itself: Ankersen et al. 1998 (PMID 9733495) reports potencies for compounds derived from it; Hansen et al. 1999 (PMID 10427162) reports a Ki, but for NN703, a different molecule; Fowkes et al. 2018 (PMID 30282322) includes ipamorelin in its panel but reports affinity for the G-7039 derivative. That check was of indexed abstracts rather than every full text, so the honest statement is that we could not resolve one — not that none exists.
Molecular identity, resolved at PubChem
The commonest error in write-ups of this pair is treating them as comparable molecules differing in some detail.
| Property | Sermorelin | Ipamorelin |
|---|---|---|
| PubChem CID | 16132413 | 9831659 |
| Molecular formula | C149H246N44O42S | C38H49N9O5 |
| Molecular weight | 3357.9 g/mol | 711.9 g/mol |
| Monoisotopic mass | 3355.8187 | 711.3857 |
| Sequence | Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 | Aib-His-D-2-Nal-D-Phe-Lys-NH2 |
| What that sequence is | Residues 1–29 of human somatoliberin (UniProt P01286), amidated | A designed pentapeptide; not a fragment of anything endogenous |
| Receptor | GHRH receptor (GHRHR) | GHS-R1a, the ghrelin receptor |
| Human half-life measured | 4.3 ± 1.4 min (PMID 7962295) | ≈ 2 h terminal (PMID 10496658) |
| Highest status ever reached | FDA-approved as GEREF; approval of both NDAs withdrawn in 2009 | Phase 2; no approval on the public record, anywhere |
| Current FDA-approved labeling | None — DailyMed returns no SPL | None — DailyMed returns no SPL |
They differ by nearly a factor of five in mass and share no sequence at all. Three of ipamorelin’s five residues are not standard L-amino acids — alpha-aminoisobutyric acid at 1, D-2-naphthylalanine at 3, D-phenylalanine at 4 — which is what a molecule designed to resist peptidases looks like. Sermorelin carries no such protection, having been copied from a hormone the body clears quickly by design. That single contrast drives the half-life section below.
Only one of them was ever an approved drug
Sermorelin was a marketed prescription drug in the United States. FDA approved GEREF (sermorelin acetate) injection at 0.05 mg base/amp under NDA 19-863 on December 28, 1990, for evaluating the ability of the somatotroph of the pituitary gland to secrete growth hormone; and GEREF at 0.5 mg and 1.0 mg base/vial under NDA 20-443 on September 26, 1997, for idiopathic growth hormone deficiency in children with growth failure. EMD Serono held both and discontinued them by letters dated July 11 and December 2, 2008. Discontinuation and de-approval are not the same event, and the page that gets this wrong usually stops at the first one: FDA withdrew approval of both NDAs effective June 18, 2009, announced in the Federal Register of May 19, 2009 (74 FR 23407).
The reason is documented rather than inferred. In a Federal Register determination published March 4, 2013 (document 2013-04827), FDA stated it had carefully reviewed its files and independently evaluated relevant literature and data for possible postmarketing adverse events, and determined these presentations were not withdrawn from sale for reasons of safety or effectiveness.
That sentence is the one most often over-read. It is a narrow administrative finding about why a product left the market — made so that generic applications referencing it could be considered — not a current approval, not a safety endorsement, and not a statement about anything beyond the two labeled indications. DailyMed today returns no structured product label for sermorelin, and none for ipamorelin either, which never had a history to lose.
What the trial record actually contains
| What was checked | Sermorelin | Ipamorelin |
|---|---|---|
| Registered trials naming the compound in the intervention field | None by that name — two records name GEREF in the intervention text | NCT00672074, NCT01280344 — both Helsinn Therapeutics (U.S.), Inc |
| What those records are | Two diagnostic stimulation studies, neither phased | Two Phase 2 trials in post-operative gastrointestinal recovery |
| Results posted to the registry | None — no record in the audit below has posted any | Neither record has posted any |
| Published human efficacy trial | Not resolved to a specific publication on this page — see below | Beck et al. 2014, PMID 25331030 |
| What the approval rested on | An FDA-reviewed dossier for two narrow indications, not a registry entry | No approval application on the public record |
| Human pharmacokinetic study | Soule et al. 1994, 10 men, PMID 7962295 | Gobburu et al. 1999, 8 men per dose, PMID 10496658 |
The sermorelin side needs spelling out rather than asserting, because the usual claim — that the registry holds no sermorelin at all — is not quite true. No record in a ClinicalTrials.gov intervention search on “sermorelin” carries sermorelin or GEREF in its intervention name field; two carry GEREF in the intervention text. Every record the search returns is placed below by what its own fields actually say.
| Records that… | Which ones, and what they say |
|---|---|
| Name GEREF in the intervention text | NCT03018886 (Helsinki University Central Hospital) records its stimulation agent as “GHRH(1-29), GEREF Serono, Italy”; NCT00324064 (Children’s Mercy Hospital Kansas City) records “GHRH(Geref)”. Both are unphased interventional diagnostic studies, both completed, neither posted results. |
| Are tesamorelin under one of its names | NCT00123253, NCT00257712, NCT00608023, NCT00850564, NCT01263717, NCT01632592, NCT02012556, NCT02196831, NCT02553603, NCT03375788, NCT06554717 — TH9507, Egrifta and tesamorelin are the same molecule. |
| Name GHRH(1-44), which is also tesamorelin | NCT00675506, whose intervention reads “growth hormone releasing hormone (GHRH) 1-44” and is other-named TH9507. |
| Are not a GHRH-receptor agonist at all | NCT01359488 studies VRS-317, a long-acting recombinant growth hormone, and matched only through a keyword list; NCT00004332 studies a GHRH antagonist in acromegaly. |
| Name no product, only “GHRH” or “GHRH plus arginine” | NCT00000380, NCT00720902, NCT00791843, NCT00795210, NCT00807365, NCT01410799, NCT02271282, NCT02507245, NCT02736591, NCT03031535 — plus NCT01060488, a validation of the GHRH-plus-arginine test sponsored by Merck KGaA, the corporate parent of the NDA holder, which still does not say which agent it used. |
The entries in that last row may well have used GHRH(1-29); they do not say so, and counting them would assume what they omit. And the chronology explains the thinness better than any judgement about evidence quality does: NDA 19-863 was approved in 1990 and NDA 20-443 in 1997, while the earliest record in this entire result set was first submitted in October 1999. Sermorelin’s approval-grade evidence was generated before there was a public registry to hold it, which is a different thing from that evidence not existing.
The ipamorelin entries need a different caveat. Both Helsinn records are genuine sponsor-filed Phase 2 trials, and the smaller was published: Beck et al., International Journal of Colorectal Disease 2014;29:1527-34, multicentre, double-blind, placebo-controlled, in bowel-resection patients — 117 enrolled, 114 analysed. Median time to tolerating a standardised solid meal was 25.3 hours against 32.6 on placebo, p = 0.15: well tolerated, no separation from placebo in the key or secondary analyses. The larger record, NCT01280344, enrolled 320, completed in May 2014, was last updated in April 2017, and has never posted results — a completed trial of that size with no results is itself a finding.
A third record surfaces on the name and should not be counted as evidence. NCT07717866, the “Trifecta Research Study” filed by Axial Therapeutic Research, is an observational cohort of 52 veterans whose interventions are EEG-guided transcranial magnetic stimulation, ibogaine with magnesium, and inhaled 5-MeO-DMT; ipamorelin appears once, at the end of a bundled “Physiological Supplementation” list alongside testosterone, anastrozole, gonadorelin, vitamins and fish oil. It was submitted in July 2026 for a study it says began in August 2022, it is that sponsor’s only filing, and nothing in an uncontrolled bundle of that shape is attributable to a single item in it.
Half-life: minutes against hours
Soule et al. (J Clin Endocrinol Metab 1994;79:1208-11, PMID 7962295) infused GHRH-(1-29)-NH2 intravenously at a constant 25 ng/kg·min in 10 normal men and measured a disappearance half-time of 4.3 ± 1.4 minutes, with a metabolic clearance rate of 39.7 ± 3.9 mL/kg·min (both mean ± SE); a D-Ala-2 analog in the same study ran 6.7 ± 0.5 minutes with clearance cut to 21 ± 1.2. Position 2 is the whole mechanism: Frohman et al. (J Clin Invest 1989;83:1533-40, PMID 2565342) identified dipeptidylpeptidase IV and trypsin-like activity as the routes by which human GHRH is degraded in plasma, DPP-IV clipping after that alanine — which sermorelin, being residues 1 through 29, carries.
Gobburu et al. (Pharm Res 1999;16:1412-6, PMID 10496658) escalated ipamorelin through five 15-minute intravenous infusion rates, eight healthy men at each level, and reported a terminal half-life of approximately 2 hours — what a sequence built from alpha-aminoisobutyric acid and D-amino acids is for. The honest caveat: separate studies five years apart, different designs and assays, never run head to head. The order-of-magnitude gap is robust; a precise ratio drawn across two such studies is not. One consequence is also often assumed backwards — half-life changes nothing about reconstitution arithmetic. Concentration is a property of what goes into the vial; half-life is a property of what happens afterwards.
Where the arithmetic actually differs
Both are commonly supplied as lyophilised powder in 5 mg and 10 mg research vials and reconstituted the same way with the same preserved diluent, so the honest answer to “does the math differ?” is: not in milligrams.
| Vial | + 1 mL diluent | + 2 mL diluent | + 3 mL diluent |
|---|---|---|---|
| 5 mg, either compound | 5 mg/mL | 2.5 mg/mL | 1.67 mg/mL |
| 10 mg, either compound | 10 mg/mL | 5 mg/mL | 3.33 mg/mL |
It differs in molecules — vial amount divided by molecular weight is what the label actually buys.
| Vial | Sermorelin | Ipamorelin | Ratio |
|---|---|---|---|
| 5 mg | 1.49 µmol | 7.02 µmol | 4.72× |
| 10 mg | 2.98 µmol | 14.05 µmol | 4.72× |
| Per milligram | 298 nmol/mg | 1405 nmol/mg | 4.72× |
Any comparison stated in milligrams therefore compares unequal numbers of molecules. It is a unit conversion, not a potency claim: it says how many molecules a label contains, not what any of them do. The reconstitution sections of the sermorelin and ipamorelin guides handle the milligram side.
One caveat applies to both. The approved GEREF presentations were labeled in milligrams of base — 0.5 mg base/vial, 0.05 mg base/amp — because milligrams of peptide base and of acetate salt are different quantities. A research vial marked with a bare milligram figure leaves that unresolved, and no arithmetic can resolve it.
What neither record supports
- No head-to-head study exists. Every figure above comes from separate publications with separate designs, so any claim that one “outperforms” the other is an inference across incomparable studies.
- Sermorelin’s approval covered two narrow indications and nothing else — a pituitary stimulation test, and idiopathic growth hormone deficiency in children with growth failure. Marketing stopped in 2008 and the approvals themselves were withdrawn effective June 18, 2009.
- Ipamorelin’s one published human efficacy trial did not meet its endpoint, and its selectivity data are preclinical — rat cells, anaesthetised rats, conscious swine.
- Neither compound has current FDA-approved labeling — worth holding onto whenever a listing quotes something that reads like one.
Medibact publishes research guides for each compound, and supplies the USP-grade bacteriostatic water used as the diluent — produced in an FDA-registered U.S. facility, research use only. Medibact is not affiliated with EMD Serono, Merck KGaA, Helsinn Therapeutics or any other organisation named here; they are named because their filings and publications are the record.
Where this sits in the rest of the reference
FAQ
What is the actual difference between sermorelin and ipamorelin?
They bind different receptors. Sermorelin is GHRH(1-29)-amide — the first 29 residues of human growth-hormone-releasing hormone — acting at the GHRH receptor. Ipamorelin is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, acting at GHS-R1a, the receptor whose endogenous ligand is ghrelin. Converging on one pituitary axis is the only thing they genuinely share.
Is sermorelin FDA approved?
It was, and it is not now. FDA approved GEREF (sermorelin acetate) injection 0.05 mg base/amp under NDA 19-863 on December 28, 1990, for evaluating the ability of the somatotroph of the pituitary gland to secrete growth hormone, and GEREF 0.5 mg and 1.0 mg base/vial under NDA 20-443 on September 26, 1997, for idiopathic growth hormone deficiency in children with growth failure. EMD Serono discontinued both in 2008 and FDA withdrew approval of both NDAs effective June 18, 2009 (74 FR 23407). DailyMed returns no structured product label for sermorelin today.
Was sermorelin withdrawn because it was unsafe?
No, and FDA said so in writing. In a Federal Register determination published March 4, 2013 (document 2013-04827), FDA stated it had reviewed its files and independently evaluated relevant literature and data for possible postmarketing adverse events, and determined the GEREF presentations were not withdrawn from sale for reasons of safety or effectiveness. That is a narrow administrative finding about why a product left the market — not a current approval, and not a safety endorsement.
Is ipamorelin FDA approved?
No. Ipamorelin has never been approved by FDA or, on the public record, by any other regulator. Its human development reached Phase 2 under Helsinn Therapeutics (U.S.), Inc for postoperative gastrointestinal recovery — ClinicalTrials.gov records NCT00672074 and NCT01280344 — and stopped there. DailyMed returns no structured product label for it either.
Which of the two has more human evidence behind it?
Neither is deep, and they are thin in different ways. Sermorelin holds something ipamorelin never obtained: an approval-grade dossier FDA reviewed, for two narrow indications. Its registry footprint is small and mostly diagnostic — two records name GEREF in their intervention text, NCT03018886 and NCT00324064, and both are stimulation-test studies — largely because both approvals predate the public registry. Ipamorelin has one published human efficacy trial, Beck et al. 2014, reporting a median 25.3 hours to first tolerated meal against 32.6 on placebo, p = 0.15. Its larger 320-participant record, NCT01280344, completed in May 2014 and has never posted results.
Why is sermorelin's half-life so much shorter than ipamorelin's?
Because of where each molecule is cut. Frohman et al. 1989 (PMID 2565342) identified dipeptidylpeptidase IV as a principal route of human GHRH degradation in plasma, clipping after the position-2 alanine — which sermorelin carries. Soule et al. 1994 measured 4.3 ± 1.4 minutes for GHRH-(1-29)-NH2 in 10 normal men, against 6.7 ± 0.5 minutes for a D-Ala-2 analog protected at that site. Ipamorelin opens with alpha-aminoisobutyric acid and carries two D-amino acids, and Gobburu et al. 1999 reported a terminal half-life near 2 hours.
Does the reconstitution math differ between them?
The milligram arithmetic is identical; the molar arithmetic is not. Concentration is vial amount divided by diluent volume, so a 5 mg vial of either compound with 2 mL of bacteriostatic water sits at 2.5 mg/mL. But sermorelin weighs 3357.9 g/mol and ipamorelin 711.9, so a milligram of ipamorelin holds about 4.72 times as many molecules. Any milligram-for-milligram comparison of the two compares unequal numbers of molecules.
Does a research vial label say whether the milligrams are peptide or salt?
Usually not, and the distinction is real: both compounds are handled as acetate salts, and acetate contributes mass that is not peptide. The approved GEREF presentations stated it on the label — 0.5 mg base/vial, 0.05 mg base/amp — because milligrams of base and of acetate salt are different quantities. A bare milligram figure with no base-or-salt statement leaves that unresolved, and no arithmetic can resolve it.
Is any of this medical, dosing or treatment guidance?
No. This page is regulatory and literature reference for research-use context only. Where it quotes a figure — an infusion rate, a trial dose, a half-life — that figure describes what a published study or an approved label reported, not a recommendation, and not a dose, route or frequency for anyone. Medibact is not affiliated with EMD Serono, Merck KGaA, Helsinn or any other organisation named here.
Educational use only — not medical advice. This guide summarizes information reported in published research and community practice for educational purposes. It is not medical advice and not a recommendation to use any compound. Any doses, schedules, or combinations shown are examples of what has been reported, not instructions for you. Many peptides described here are research compounds that are not FDA-approved for the uses discussed and may be investigational or restricted. Effects, risks, and legal status vary; individual needs and results vary. Consult a qualified, licensed healthcare professional before making any decision. Do not use this content to diagnose, treat, or dose yourself.