Sermorelin Research

Most research peptides sit in one of two regulatory categories: approved by a drug regulator, or never approved. Sermorelin sits in a third. It held two US approvals, both withdrawn at the sponsor's own request, and neither has existed since June 2009.^[2][3] "Sermorelin is FDA approved" is false, and "sermorelin was never FDA approved" is equally false.

What sermorelin is

Sermorelin is human growth hormone releasing hormone 1-29, the N-terminal 29-residue fragment of the 44-residue hypothalamic hormone, amidated at the C-terminus.^[1] The product declares CAS 86168-78-7, formula C149H246N44O42S and a molecular weight of 3,357.93. That CAS resolves on PubChem to CID 16132413 under the name sermorelin, and the declared formula matches that record exactly.^[1]

GRF(1-29) and GHRH(1-29) name the same molecule, so the product name is internally consistent.^[1] One similar name belongs to a different molecule entirely. Mod GRF 1-29, also sold as CJC-1295 without DAC, carries four amino acid substitutions and is a distinct entity with no approval history of any kind. Nothing here transfers to it. Sermorelin sold for research is bulk material, not a finished medicine.

The two approvals, and how they ended

FDA approved NDA 019863 on 28 December 1990, sponsor EMD Serono, brand GEREF, for "evaluating the ability of the somatotroph of the pituitary gland to secrete growth hormone."^[2][3] That indication is a diagnostic provocative test, not a therapy. FDA then approved NDA 020443 on 26 September 1997, same sponsor and brand, for treatment of idiopathic growth hormone deficiency in children with growth failure.^[2][3] The two indications were different, and vendor pages routinely cite the 1990 diagnostic approval as though it endorsed treatment.

Of the two indications, the diagnostic one has the better evidence behind it. A 1999 narrative review reports intravenous sermorelin as a rapid and relatively specific provocative test in humans.^[10] It produced fewer false-positive growth hormone responses in children without growth hormone deficiency than other provocative tests did.^[10] The same review of human data states the decisive limitation: a normal growth hormone response to intravenous sermorelin cannot exclude growth hormone deficiency of hypothalamic origin.^[10] A subnormal response to a different provocative test is still required to confirm the disease.^[10]

EMD Serono notified FDA on 11 July 2008 that the diagnostic product was being discontinued.^[3] A letter of 2 December 2008 discontinued the therapeutic product and requested withdrawal of NDA 020443.^[3] A further letter of 12 December 2008 requested withdrawal of NDA 019863, and FDA withdrew both applications effective 18 June 2009.^[3] All three products carry marketing status Discontinued in FDA's database today.^[2] That database also lists two labeling supplements on the diagnostic application, approved in March 1998 and October 2001.^[2] What those labeling changes said cannot be read from that database, because approved label text is not posted there for products withdrawn before 2009.^[2]

What FDA determined in 2013

On 4 March 2013 FDA published a determination that these products "were not withdrawn from sale for reasons of safety or effectiveness."^[3] The same finding is carried in the Drugs@FDA product records.^[2] Why the products actually left the market is a separate question. The Federal Register notice records the discontinuation and withdrawal requests while giving no commercial rationale.^[3] Claims that recombinant growth hormone outcompeted it, or that the ingredient became hard to source, appear in neither that notice nor the Drugs@FDA record.^[2][3] The competition claim does appear in a 2006 editorial discussed below.^[17] The commercial reason is undocumented in the primary regulatory record.

The determination began outside FDA. A citizen petition dated October 2012 requested it, under docket FDA-2012-P-1071, and the petitioner is named in the notice.^[3] FDA extended the finding to the diagnostic product on its own initiative.^[3] The legal purpose of such a determination is to let generics be approved.^[3] FDA's database lists exactly two applications ever attached to this ingredient, both of them the original NDAs.^[2] No generic has been filed in the thirteen years since that determination, and no FDA-approved sermorelin product has existed in the United States since 18 June 2009.^[2]

What the orphan record adds

The 1997 therapeutic approval was an orphan approval, designated in September 1988 for idiopathic or organic growth hormone deficiency in children with growth failure, with exclusivity ending in September 2004.^[4] The designation is the broader of the two, since the approval that followed it covers idiopathic growth hormone deficiency alone.^[2][3][4] An orphan approval covers a rare disease population, and it is not a general therapeutic endorsement. Two further designations went nowhere: an ovulation-induction adjunct from February 1990, and AIDS-associated catabolism and weight loss from December 1991.^[4] Both are recorded as never approved for the orphan indication, and both were later withdrawn or revoked.^[4]

Mechanism, and the desensitization problem

Sermorelin is an agonist at the pituitary GHRH receptor, raising endogenous growth hormone and, downstream, IGF-1.^[10] One mechanistic problem is that the response can fade. Six children with partial growth hormone deficiency showed a biphasic response to continuous exposure.^[5] Integrated 24-hour growth hormone rose early, then fell by three months and further by six to near baseline.^[5] Pulse amplitude and frequency were both altered in that human study, and one child had complete suppression of growth hormone secretion by the end.^[5] Two further results from the same six children were negative: no correlation between those hormone changes and height velocity, and three of the six did not grow significantly.^[5] A separate 12-month human study found overnight growth hormone levels and responses to GHRH testing both falling during therapy.^[12] Somatotroph desensitization on sustained exposure is documented in those two human studies, not theoretical.^[5][12] A third human trial found priming rather than desensitization on one arm.^[8] Growth hormone responses to an intravenous GHRH test showed a priming effect in the lower divided-dose sermorelin arm, while responses fell in the growth hormone arm.^[8] The direction of the pituitary response is therefore not uniform across schedules.^[5][8][12]

The human trials in children

The registration-era study was a multicenter open-label trial in 110 previously untreated prepubertal children with growth hormone deficiency, run by the Serono-sponsored Geref International Study Group.^[6] Mean height velocity rose from 4.1 cm/year at baseline to 8.0 at six months, then fell back to 7.2 at twelve.^[6] Three limits travel with that result. There was no control arm, only 86 of the 110 enrolled were evaluable, and the endpoint was height velocity rather than final adult height.^[6] That human trial also recorded no change in fasting glucose and no excessive generation of IGF-1, and reported the treatment as well tolerated.^[6]

Three of the trials in children set sermorelin against growth hormone, and none of the three favored sermorelin.^[7][8][9] Two of them were randomized parallel comparisons.^[7][8] The third was a before-after study in which every child took sermorelin for one year and then switched to growth hormone for the following year.^[9] A randomized three-arm trial in 60 children gave mean height velocities of 9.2 and 9.3 cm/year on two sermorelin arms against 14.6 on growth hormone, p<0.01.^[7] In that same human trial serum IGF-1 rose initially, then fell back to values similar to those before treatment.^[7] Those authors concluded the treatment was unlikely to be as effective as growth hormone.^[7] A randomized trial in 43 children found height velocity lowest in the lower-dose arm and comparable between the higher-dose and growth hormone arms.^[8] On the harder endpoint, height standard deviation score for bone age increased only in the growth hormone group.^[8] In nine children with radiation-induced deficiency, height velocity was 3.3 cm/year before treatment, 6.0 on sermorelin and 7.5 on growth hormone.^[9] Those three figures come from three consecutive periods in the same children, so the growth hormone year is confounded by age and by treatment order.^[9] Bone age advanced by a mean of 1.1 years per chronological year during the sermorelin year in that human trial.^[9] The same trial reported no adverse changes in biochemical or hormonal analyses, and no adverse events attributable to sermorelin.^[9]

A 1999 narrative review states that the recommended regimen was never directly compared with somatropin, and that the comparisons which exist used continuous infusion or divided daily doses.^[10] Continuous infusion produced the biphasic desensitization result, and one divided-dose study found overnight growth hormone falling across twelve months.^[5][12] The comparative loss is real, and it is confounded by schedule.

That same review reads the pediatric data more favorably than the head-to-head trials do.^[10] It reports height velocity increases sustained across twelve months, catch-up growth in the majority of treated children, and data in a few children suggesting maintenance to 36 months.^[10] It is a secondary source from a commercial drug-profile publisher, and it states the effect on final adult height remained undetermined.^[10]

Negative and null findings

An intranasal formulation failed cleanly in humans. Across eight short prepubertal children the knemometric growth rate rose at six weeks, p=0.03, then declined rapidly, while the six-month stadiometric height velocity did not increase at all.^[11] Growth hormone peak amplitudes were variably reduced by six weeks, and reduced further by six months.^[11] That six-week reduction was reported in most patients rather than all.^[11] Three of eight developed GHRH antibodies from a negative baseline, and treatment was stopped in two.^[11] Local tolerance was good in one child, while most of the others reported sneezing immediately after insufflation, rhinorrhea and mild mucosal burning.^[11] The authors attributed unsuitability to decreasing absorption and effectiveness, antibody development and local reactions.^[11] They concluded that intranasal GHRH was not suitable in its present form for use in children.^[11]

Immunogenicity was near-universal in one human trial.^[7] All 20 children on the higher-dose arm and 19 of 20 on the lower-dose arm developed anti-GHRH antibodies, with no growth hormone antibodies detected.^[7] Titers had almost disappeared nine months after stopping, and no correlation was found between antibody titer and height gain.^[7] No serious side effects were seen in that trial, and three children reported mild irritation at the injection site.^[7] A separate human trial reported accumulating circulating GHRH immunoreactivity in its higher-dose arm, which is measured peptide rather than antibody.^[8]

One trial measured growth after treatment stopped, and the gain reversed.^[12] Seventeen short children who were not growth hormone deficient completed twelve months of treatment.^[12] Height velocity rose from 4.8 to 7.2 cm/year, then fell to 3.89 cm/year in the first three months off therapy.^[12] By six and twelve months off therapy it was no different from pretreatment values.^[12] That same human study recorded fasting blood glucose, insulin and IGF-1 all rising during treatment.^[12] The 1999 review reports transient facial flushing and injection-site pain as the most commonly reported adverse events.^[10]

One post-marketing record sits outside the trials. FDA's adverse event reporting system holds 59 human reports naming sermorelin as the medicinal product.^[21] A report in that system records a suspicion rather than a demonstrated cause.^[21] The count alone establishes no adverse effect of sermorelin.^[21]

None of the human trials published between 1993 and 1997 measured final adult height, and a targeted PubMed search returns no study that did.^[20] Every efficacy figure in those trials is a surrogate for that endpoint. A PubMed search for systematic reviews or meta-analyses of sermorelin returns zero records.^[20]

Evidence that belongs to other molecules

The best-known "GHRH" results are not sermorelin results. The human trial showing cognitive benefit in mild cognitive impairment used tesamorelin supplied by its manufacturer Theratechnologies, and the abstract names both compound and company.^[13] Tesamorelin is a 44-mer with an N-terminal acyl group and it holds a live FDA approval, while sermorelin's is dead. Nothing from that literature transfers.

The aging-adult trials cited on sermorelin sales pages also used a different compound, since both gave [Nle27]GHRH(1-29)-NH2, a norleucine-substituted analog.^[14] They were single-blind, ran five months, and drew on one cohort of 19 people aged 55 to 71.^[14] They are not independent replications of each other.^[14] The registry compounds the confusion. Some records returned by a sermorelin query name the intervention only as GHRH, and others name molecules that are not sermorelin at all.^[15] At least two completed records name tesamorelin or its development code TH9507.^[15] Other completed records name molecules that are not GHRH analogs at all, among them somatropin, octreotide acetate and toremifene.^[15] Two registered GHRH trials in older adults were terminated at 13 and 5 participants, for stated reasons of funding ending and the principal investigator leaving.^[15]

Only one clinical paper gives actual sermorelin to adults seeking body-composition change.^[16] It is a retrospective review of records from men on testosterone therapy, 105 screened and 14 analyzed, who received sermorelin with two other secretagogues.^[16] IGF-1 rose. Attribution to sermorelin is impossible from that design, and IGF-1 is a surrogate rather than an outcome.^[16] Those authors declared no conflicts of interest.^[16]

Conflicts inside this literature

The most-cited source in favor of sermorelin on anti-aging pages is not a study.^[17] PubMed types it as an editorial, it runs two pages, and it carries no abstract and no primary data.^[17] Its closing paragraph carries an offer.^[17] The Society for Applied Research in Aging would supply sermorelin free of cost to practitioners willing to study its effects and report the outcomes in a peer-reviewed journal.^[17] The editorial names Clinical Interventions in Aging, the journal it appears in, as an example of such a venue.^[17] The author's listed affiliation is that society.^[17] The editorial is also where the recombinant-growth-hormone competition narrative appears.^[17] The original trial program was sponsored by Serono, which is normal for registration work.^[6]

Where the record stands

The therapeutic evidence base is thin. Seven human trials in children, published between 1993 and 1997, are essentially all of it, and none enrolled more than 110.^{[5][6][7][8][9][11][12]} Most of the 331 PubMed records naming sermorelin use it as a diagnostic reagent rather than studying it as a therapy.^[20] No completed trial in aging adults has been identified as using sermorelin itself.^[15] A completed registry trial of GHRH for age-related sleep, for instance, lists its intervention only as GHRH with no molecule specified.^[15] Sermorelin does not appear in the 503A bulk drug substances list at 21 CFR 216.23.^[19] As of the 2026 Prohibited List it is named among growth hormone releasing factors and prohibited at all times.^[18]

Two 2026 narrative reviews describe what sermorelin now is in practice. They place it inside a class of unregulated peptides sold as research compounds to modulate the growth hormone axis.^[22] Named alongside it in that class are tesamorelin, the CJC-1295 analogs, the growth hormone releasing peptides, hexarelin, ipamorelin and AOD9604.^[22] Those reviews catalogue adverse effects reported in humans across that class, including prolactin and cortisol elevations and metabolic disturbance.^[22] Those effects are pooled across a heterogeneous class, so none of them is a sermorelin-specific figure.^[22] Research material is supplied for laboratory research use only and is not for human consumption.

Frequently Asked Questions

Is sermorelin FDA approved?

No, and "never approved" is equally wrong. FDA approved NDA 019863 in 1990 as a diagnostic provocative-test agent, and NDA 020443 in 1997 for idiopathic growth hormone deficiency in children with growth failure.^[2][3] Both were withdrawn at the sponsor's request, effective 18 June 2009, and no FDA-approved sermorelin product has existed since.^[2][3] FDA determined in 2013 that the products were not withdrawn for reasons of safety or effectiveness.^[3]

Why was it withdrawn, then?

The documented part is the negative finding: not for safety or effectiveness.^[3] The affirmative commercial reason is undocumented in the primary regulatory record. FDA's notice records the sponsor's discontinuation and withdrawal requests while giving no rationale.^[3] The competition explanation appears in a 2006 editorial rather than in any regulator's record.^[17]

Do the GHRH trials in aging and cognition apply to sermorelin?

No, on the evidence available. The human trial in mild cognitive impairment used tesamorelin supplied by its manufacturer, and the aging-adult trials used [Nle27]GHRH(1-29)-NH2.^[13][14] Registry records returned by a sermorelin query often name the intervention only as GHRH, and others name molecules that are not sermorelin at all.^[15] No completed trial in aging adults has been identified as using sermorelin itself.^[15]

Is GRF 1-29 the same as Mod GRF 1-29?

No, they are different molecules with different regulatory histories. Mod GRF 1-29, also sold as CJC-1295 without DAC, carries four amino acid substitutions and is a distinct entity with no approval history of any kind. Sermorelin's regulatory record belongs to sermorelin alone and does not extend to it.

References

1. 1

   PubChem Compound record CID 16132413, sermorelin, CAS 86168-78-7; National Library of Medicine. CAS and name queries were round-tripped against PUG-REST, 28 August 2026. PUG-REST returns MolecularFormula C149H246N44O42S and MolecularWeight 3357.9, the latter at one decimal place.
2. 2

   US Food and Drug Administration, Drugs@FDA. NDA 019863 and NDA 020443, sponsor EMD Serono, brand GEREF; retrieved via the openFDA drug/drugsfda endpoint, 28 August 2026. Two applications and three products, all marketing status Discontinued, each strength field carrying the Federal Register determination text.
3. 3

   US Food and Drug Administration. Determination That GEREF (Sermorelin Acetate) Injection, 0.5 Milligrams Base/Vial and 1.0 Milligrams Base/Vial, and GEREF (Sermorelin Acetate) Injection, 0.05 Milligrams Base/Amp, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. 78 FR 14095, 4 March 2013, document 2013-04827, Docket No. FDA-2012-P-1071. Full text retrieved from govinfo.gov, 28 August 2026.
4. 4

   US Food and Drug Administration, Office of Orphan Products Development. Orphan drug designation records for sermorelin acetate, sponsor EMD Serono: designation 24687 (designated 14 September 1988, Designated/Approved, marketing approval 26 September 1997, exclusivity end 26 September 2004); designation 31988 (designated 13 February 1990, ovulation induction adjunct, not FDA approved for the orphan indication, designation withdrawn or revoked); designation 61491 (designated 5 December 1991, AIDS-associated catabolism and weight loss, not FDA approved for the orphan indication, designation withdrawn or revoked). Retrieved 28 August 2026.
5. 5

   Tauber MT, Pienkowski C, Pigeon P, Cataldi M, Rochiccioli P. Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency. Acta Paediatr Suppl. 1993;388:28-30; discussion 31. PMID 8329829.
6. 6

   Thorner M, Rochiccioli P, Colle M, et al; Geref International Study Group. Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. J Clin Endocrinol Metab. 1996;81(3):1189-1196. PMID 8772599.
7. 7

   Chen RG, Shen YN, Yei J, et al. A comparative study of growth hormone (GH) and GH-releasing hormone(1-29)-NH2 for stimulation of growth in children with GH deficiency. Acta Paediatr Suppl. 1993;388:32-35; discussion 36. PMID 8329830.
8. 8

   Neyzi O, Yordam N, Ocal G, et al. Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl. 1993;388:16-21; discussion 22. PMID 8329826.
9. 9

   Ogilvy-Stuart AL, Stirling HF, Kelnar CJ, et al. Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone. Clin Endocrinol (Oxf). 1997;46(5):571-578. PMID 9231053.
10. 10

    Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999;12(2):139-157. PMID 18031173. A narrative drug profile from a commercial publisher, cited here as a secondary source.
11. 11

    Hümmelink R, Sippell WG, Benoit KG, Danielson K, Faijerson Y. Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth. Acta Paediatr Suppl. 1993;388:23-26; discussion 27. PMID 8329828.
12. 12

    Kirk JM, Trainer PJ, Majrowski WH, Murphy J, Savage MO, Besser GM. Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clin Endocrinol (Oxf). 1994;41(4):487-493. PMID 7955460.
13. 13

    Baker LD, Barsness SM, Borson S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012;69(11):1420-1429. PMID 22869065. The abstract identifies the intervention as tesamorelin (Theratechnologies Inc).
14. 14

    Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab. 1997;82(5):1472-1479. PMID 9141536. Companion paper on immune measures from the same cohort: Khorram O, Yeung M, Vu L, Yen SS. J Clin Endocrinol Metab. 1997;82(11):3590-3596. PMID 9360512.
15. 15

    ClinicalTrials.gov, API v2, query.term=sermorelin, retrieved 28 August 2026; the query returns 42 records. Records cited here: NCT01410799 (terminated, 13 enrolled, "Funding ended"), NCT00807365 (terminated, 5 enrolled, "PI left JHU"), NCT00257712 (completed, intervention TH9507, the development code for tesamorelin) and NCT00850564 (completed, intervention named as tesamorelin). The same query returns completed records whose named intervention is neither sermorelin nor a GHRH analog, among them NCT01359488 (VRS-317), NCT00448747 (AEZS-130 / macimorelin), NCT01088412 (somatropin), NCT03031535 (octreotide acetate), NCT01897844 (ITF2984) and NCT02271282 (toremifene). Of the 42 records, 28 carry status Completed. It also returns completed records whose only named intervention is "GHRH" with no molecule specified, including NCT00000380, "Growth Hormone Releasing Hormone (GHRH) Treatment for Age-Related Sleep...", status Completed.
16. 16

    Sigalos JT, Pastuszak AW, Allison A, et al. Growth hormone secretagogue treatment in hypogonadal men raises serum insulin-like growth factor-1 levels. Am J Mens Health. 2017;11(6):1752-1757. PMID 28830317. The authors declared no conflicts of interest.
17. 17

    Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006;1(4):307-308. PMID 18046908; PMC2699646. PubMed publication type Editorial. Full text retrieved from PMC, 28 August 2026; the free-supply statement and the author's society affiliation are quoted from that text, which reads "to report the outcomes in a peer-reviewed journal such as Clinical Interventions in Aging."
18. 18

    World Anti-Doping Agency. The 2026 Prohibited List, section S2 (peptide hormones, growth factors, related substances and mimetics), which sits under substances prohibited at all times. Sermorelin is named among growth hormone releasing factors.
19. 19

    21 CFR 216.23, Bulk drug substances that can be used to compound drug products in accordance with section 503A. Full current text retrieved from the eCFR API, 28 August 2026; sermorelin appears nowhere in Part 216.
20. 20

    PubMed searches via NCBI E-utilities, 28 August 2026. "sermorelin AND (systematic review[pt] OR meta-analysis[pt])" returns 0 records. "sermorelin AND final adult height" returns 2 records, neither of which is a sermorelin final-height study: PMID 10594520 (20 tall versus 20 short postpubertal men aged 18 to 27, abstract naming the agent as GHRH) and PMID 18031173 (the BioDrugs review). "sermorelin" returns 331 records, most using it as a diagnostic reagent rather than studying it as a therapy.
21. 21

    US Food and Drug Administration Adverse Event Reporting System, retrieved via the openFDA drug/event endpoint, 28 August 2026. The query patient.drug.medicinalproduct:"SERMORELIN" returns 59 reports. The openfda.generic_name form of the same query returns NOT_FOUND, which is the same annotation-block false negative that affects the Drugs@FDA queries in reference 2. FAERS reports are spontaneous and uninvestigated, and carry no causal assessment.
22. 22

    Dominikowski A, et al. Front Endocrinol (Lausanne). 2026. PMID 42395176. Second review: Mendias CL, et al. Sports Med. 2026. PMID 41966639. Both are narrative reviews and are cited here as secondary sources for class characterization only; their reported adverse effects are pooled across a heterogeneous group of growth hormone secretagogues and are not sermorelin-specific.