Peptides

Sermorelin: the FDA record, the growth-hormone evidence, and where it legally sits now

By the US Health Digest editorial team · Published September 2, 2026 · Every claim linked to its primary source

Sermorelin acetate was an approved US drug: Geref Diagnostic under NDA 19-863, approved December 28, 1990, and Geref under NDA 20-443, approved September 26, 1997, both held by EMD Serono and both withdrawn effective June 18, 2009. On March 4, 2013, FDA determined both products "were not withdrawn from sale for reasons of safety or effectiveness" — the same question the 21 CFR 216.24 prohibited-compounding list turns on; sermorelin is not on that list. It sits in Category 1 of FDA's 503B nominated-bulks list, and on no 503A list.

The regulatory record, which is more interesting than the marketing

Sermorelin is not a research chemical with no paperwork. It is a 29-amino-acid growth-hormone-releasing hormone analogue that went through the full US approval process twice, and the documents survive.

The Federal Register notice of March 4, 2013 (78 FR 14095) sets out the whole sequence. The 0.05 mg base/amp product, NDA 19-863, "is indicated for evaluating the ability of the somatotroph of the pituitary gland to secrete growth hormone" — a diagnostic agent. The 0.5 mg and 1.0 mg base/vial product, NDA 20-443, "is indicated for the treatment of idiopathic growth hormone deficiency (GHD) in children with growth failure." EMD Serono notified FDA that the products were being discontinued — the diagnostic product in a letter dated July 11, 2008, the treatment product in a letter dated December 2, 2008 — and requested withdrawal of NDA 20-443 in that December 2 letter and of NDA 19-863 in a further letter dated December 12, 2008. FDA withdrew both approvals in 74 FR 23407, effective June 18, 2009.

Four years later a citizen petition (Docket No. FDA-2012-P-1071) asked FDA to say why. FDA reviewed its files, and stated that it had "also independently evaluated relevant literature and data for possible postmarketing adverse events for both GEREF products," then determined under 21 CFR 314.161 that neither had been withdrawn for reasons of safety or effectiveness. That is a specific legal finding, not a general endorsement: its stated effect is that "[t]his determination will allow FDA to approve abbreviated new drug applications (ANDAs)" referencing the discontinued products. FDA's Drugs@FDA record still carries the annotation on both listings, and both remain marked Discontinued.

What that determination does and does not permit

Two separate FDA lists decide whether a substance can be compounded, and sermorelin lands differently on each.

21 CFR 216.24 names drug products that "were withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective," and which "may not be compounded" under the 503A or 503B exemptions. We read the full current text of the section on September 2, 2026 — roughly 90 entries, from adenosine phosphate to zomepirac sodium. Sermorelin is not among them, and neither is any growth hormone or GHRH product. That absence is consistent with the 2013 determination, which answered the same question — withdrawal for safety or effectiveness — in the negative.

FDA's nominated-bulks category lists are the other half, and they are where the picture gets specific. On the 503B list (outsourcing facilities), updated March 21, 2025, "Sermorelin Acetate" appears in Category 1 with two asterisks — a marker FDA defines in its own footnote: "Bulk drug substances in category 1 that are components of FDA-approved drugs are designated with two asterisks (**) below." FDA's compounding page states that it "does not intend to take action against an outsourcing facility for compounding drugs using bulk drug substances identified in category 1 provided that the conditions described in the guidance document are met." Category 1 is an enforcement posture and a place in an unfinished evaluation, not a finding that the substance is approved or that any product made from it is lawful; FDA has published no document applying that posture to sermorelin specifically.

On the separate 503A list (retail compounding pharmacies), updated May 14, 2026, sermorelin does not appear at all — not in Category 1, not in Category 2, not in Category 3. We searched the full extracted text and found zero occurrences. That is a different posture from the peptides it is usually stacked with: on the 503B list, GHRP-6, ibutamoren mesylate and ipamorelin acetate sit in Category 2, "Bulk Drug Substances that Raise Significant Safety Risks," and GHRP-2 is split — Category 2 for injectable and nasal routes of administration, Category 1 for the rest. Our guide to CJC-1295 and ipamorelin covers those separately, and the structure of the whole nomination scheme — including why leaving a category is not the same as being cleared — is set out in full there.

Enforcement has not stopped. FDA's warning letter to Xcel Research LLC, dated December 10, 2024, lists SERMORELIN among seven products offered on the firm's website and states that "your products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d)," adding that "evidence obtained from your website establishes that your products are intended to be drugs for human use."

What has actually been studied

FDA said it plainly in its own briefing document for the Pharmacy Compounding Advisory Committee meeting of October 29, 2024: "Among GHSs such as ipamorelin, only sermorelin (Geref, NDA 020443) was approved for the treatment of short stature associated with GHD in pediatric patients," and "There are no GHSs that have been approved for the treatment of either adult- or childhood-onset GHD in adults."

The published trial base is thin and old. A PubMed search for the term sermorelin in title or abstract, run September 2, 2026, returned 24 records in total; restricting that to the clinical-trial or randomised-controlled-trial publication types returned zero. Eleven of the 24 are doping-control assay-development papers. That zero is partly an indexing artefact and we say so: the randomised trials below are indexed under the chemical name GHRH(1-29)-NH₂, which is why a search on the word sermorelin does not return them. The studies below are the substantive human ones, and note the distinction in the second column: two of them used [Nle27]GHRH(1-29)-NH₂, a norleucine-substituted variant, not sermorelin itself.

What is claimed versus what is shown

The pitch is mechanistic and it is not fabricated: sermorelin acts on the pituitary to release the body's own growth hormone in pulses, rather than delivering recombinant GH from outside. Clinics extrapolate from that to muscle, fat loss, sleep and recovery. FDA catalogued the claim set itself in the 2024 PCAC briefing document, recording that websites marketing these peptides assert uses "including weight management, hormone replacement therapy, increasing vitality and mental clarity, strengthening the cardiovascular and immune system, increasing sex drive, improving recovery and repair from injuries."

Set against the table above, the gap is in the endpoints. Every adult study measured surrogates — GH pulse amplitude, IGF-I, IGFBP-3, lymphocyte counts. The one adult study that also ran DXA found lean body mass rose in men and not in women, with no other change in body composition or bone mineral density, and sleep quality unchanged in both. Nineteen people, sixteen weeks, in 1997. No adult trial of sermorelin has reported strength, walking speed, injury healing time, or any clinical outcome. And the closest thing to a clean comparison — the paediatric head-to-head — went the other way.

The most-cited piece arguing sermorelin is preferable to GH in adults, a 2006 article in Clinical Interventions in Aging, is indexed in PubMed with the publication type Editorial and carries no abstract. It is an argument, not a result.

The GLP-1 "muscle preservation" add-on: what we searched

Sermorelin is increasingly offered alongside GLP-1 medication as a way to hold onto lean mass during weight loss. Because that is an absence claim, we tested it adversarially and record the queries.

• PubMed, September 2, 2026: sermorelin AND (semaglutide OR tirzepatide OR GLP-1) — 0 results.
• PubMed: (sermorelin OR GHRH) AND (semaglutide OR tirzepatide OR GLP-1 receptor agonist) — 2 results, neither a sermorelin trial: a peptide-synthesis chemistry paper and a study of DPP-4 inhibition and the GH/IGF-I axis.
• ClinicalTrials.gov: sermorelin AND semaglutide — 0; sermorelin AND tirzepatide — 0; sermorelin AND GLP-1 — 2, neither testing sermorelin with a GLP-1.
• ClinicalTrials.gov intervention search for sermorelin returned 27 studies. We listed the intervention names on all 27: not one names sermorelin. They are tesamorelin, generic GHRH, and stimulation-test protocols.

So: no trial has tested whether sermorelin preserves lean mass during GLP-1 treatment. The instructive comparison is tesamorelin, a different GHRH analogue that did earn a US approval for a body-composition indication — Egrifta, approved November 10, 2010. Its current label indicates it "for the reduction of excess abdominal fat in HIV-infected adult patients with lipodystrophy," and then says: "EGRIFTA SV is not indicated for weight loss management as it has a weight neutral effect." The GHRH analogue that cleared FDA for fat reduction is labelled weight-neutral. What the GLP-1 lean-mass evidence actually shows — and how little of it measures function — is in our page on GLP-1 drugs and muscle loss.

Safety, and the IGF-1 question handled carefully

No sermorelin product currently has a US label: a DailyMed search on September 2, 2026 returned zero structured product labels for sermorelin, and Drugs@FDA posts no approved labelling documents for either withdrawn application. The nearest current primary document is the tesamorelin label, and it is candid. It warns that the drug "induces the release of endogenous growth hormone (GH), a known growth factor," instructs prescribers "[d]o not treat patients with active malignancy," and states that it "stimulates GH production and increases serum IGF-1, a growth factor. The effects of prolonged elevations in IGF-1 levels are unknown." Its most common adverse reactions above 5% are "[a]rthralgia, injection site erythema, injection site pruritus, pain in extremity, peripheral edema, and myalgia."

From the sermorelin literature itself: the 1993 paediatric trial reported that "[n]o serious side-effects were seen, but three patients receiving GHRH(1-29)-NH2 reported mild irritation at the injection site" — while 39 of 40 treated children developed antibodies to GHRH. The 1997 adult study reported that "[t]he only adverse side-effect was transient hyperlipidemia, which resolved by the end of the study." FDA's 2024 briefing document describes a FAERS report of a 46-year-old man who used a compounded ipamorelin-and-sermorelin combination and developed elbow arthralgia that persisted after stopping; FDA noted the combination made attribution impossible.

On cancer, the honest position is uncertainty in one direction. Higher circulating IGF-I is associated with cancer risk in observational data: in 199,698 men in UK Biobank, each 5 nmol/L increment in IGF-I carried a hazard ratio of 1.09 (95% CI 1.05–1.12) for prostate cancer diagnosis and 1.15 (1.02–1.29) for prostate cancer mortality, with Mendelian randomisation pointing the same way. That is an association between measured IGF-I and risk in untreated men — not a measurement of what a drug that raises IGF-I does. No sermorelin study has ever measured a cancer endpoint, and none was long enough to. The label of the one approved analogue treats the uncertainty as material enough to contraindicate active malignancy.

Questions worth raising with a prescriber

• Which legal route is this product coming through — a 503B outsourcing facility, a 503A pharmacy, or neither? The three have different lists behind them, and only one names sermorelin.
• What outcome will be measured, and when? IGF-1 is a surrogate; every adult study stopped there.
• Is it a single substance or a combination? The FAERS case above, and the 2017 chart review, both involved stacks in which nothing could be attributed to sermorelin.
• What does the arrangement cost over a year, and what is included? Our survey of what peptide clinics actually charge found published prices vary widely and are often quoted per month.
• Does a malignancy history change the calculation? The tesamorelin label contraindicates active malignancy, and says any preexisting malignancy should be inactive and its treatment complete before therapy starts.

Frequently asked questions

Is sermorelin FDA approved?

Not now. It was: Geref Diagnostic (NDA 19-863) was approved December 28, 1990 and Geref (NDA 20-443) on September 26, 1997, both held by EMD Serono. FDA withdrew both approvals effective June 18, 2009 at the sponsor's request. Drugs@FDA lists both as Discontinued. No sermorelin product has a current US label.

Was Geref withdrawn because it was unsafe or did not work?

No. FDA determined on March 4, 2013, in response to a citizen petition, that both Geref products "were not withdrawn from sale for reasons of safety or effectiveness." The sponsor had discontinued them commercially in 2008. Sermorelin does not appear on the 21 CFR 216.24 list of drug products withdrawn or removed for reasons of safety or effectiveness, which we read in full on September 2, 2026.

Can a pharmacy legally compound sermorelin?

The lists differ by route. "Sermorelin Acetate" is in Category 1 of FDA's 503B nominated-bulks list for outsourcing facilities, updated March 21, 2025, flagged as a component of an FDA-approved drug; FDA states it does not intend to act against an outsourcing facility compounding from Category 1 substances where the guidance conditions are met. Sermorelin appears nowhere on the 503A category lists updated May 14, 2026. None of that makes a product bought from a website lawful: FDA's December 10, 2024 warning letter to Xcel Research names sermorelin among products it called unapproved new drugs.

Does sermorelin build muscle or protect lean mass on a GLP-1?

No trial has tested it. Our PubMed search for sermorelin with semaglutide, tirzepatide or GLP-1 returned zero results on September 2, 2026, and ClinicalTrials.gov returned no study testing sermorelin alongside a GLP-1. In the one adult study that scanned body composition, 19 people aged 55 to 71 over 16 weeks, lean body mass rose in the men and not in the women, with no other change in body composition.

What side effects have been reported?

In the 1993 paediatric trial, no serious side effects, mild injection-site irritation in three patients, and GHRH antibodies in 39 of 40 treated children. In the 1997 adult study, transient hyperlipidaemia that resolved. For the class, the tesamorelin label lists arthralgia, injection-site erythema and pruritus, pain in extremity, peripheral oedema and myalgia above 5%, warns of fluid retention and glucose intolerance, and contraindicates active malignancy.

Sources

• FDA. Determination That GEREF (Sermorelin Acetate) Injection… Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness. 78 FR 14095, March 4, 2013; Docket No. FDA-2012-P-1071. Link.
• FDA. Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications. 74 FR 23407, May 19, 2009 — lists NDA 19-863 Geref Diagnostic and NDA 20-443 Geref, effective June 18, 2009. Link.
• 21 CFR 216.24 — drug products withdrawn or removed from the market for reasons of safety or effectiveness; full text as of August 31, 2026 (eCFR). Sermorelin does not appear. Link.
• FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503B, category list updated March 21, 2025 — Sermorelin Acetate in Category 1, double-asterisked; GHRP-6, ibutamoren mesylate and ipamorelin acetate in Category 2, and GHRP-2 in Category 2 for injectable and nasal routes and in Category 1 for other routes. Link.
• FDA. Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act — category 1 enforcement posture; page content current as of January 7, 2025. Link.
• FDA. 503A nominated bulk drug substances category list, updated May 14, 2026 — contains no sermorelin entry. Link.
• FDA. Briefing Document, Pharmacy Compounding Advisory Committee Meeting, October 29, 2024 (ipamorelin-related bulk drug substances) — statements on sermorelin's approval history, marketed claims, and a FAERS case. Link.
• FDA. Warning letter to Xcel Research LLC, 694608, December 10, 2024. Link.
• DailyMed. EGRIFTA SV (tesamorelin) prescribing information, SPL version 9, effective July 29, 2026. Link.
• Comparative study of GH and GHRH(1-29)-NH2 in children with GH deficiency. Acta Paediatr Suppl 1993. PMID 8329830. Link.
• Growth response to GHRH(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl 1993. PMID 8329826. Link.
• Endocrine and metabolic effects of long-term administration of [Nle27]GHRH(1-29)-NH2 in age-advanced men and women. J Clin Endocrinol Metab 1997. PMID 9141536. Link.
• Effects of [norleucine27]GHRH(1-29)-NH2 on the immune system of aging men and women. J Clin Endocrinol Metab 1997. PMID 9360512. Link.
• Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum IGF-1 Levels. Am J Mens Health 2017. PMID 28830317. Link.
• Circulating IGF-I, testosterone and prostate cancer risk in 200,000 men in UK Biobank. Int J Cancer 2021. PMID 33252839. Link.
• ClinicalTrials.gov NCT01060488 — comparative validation of the GHRH and arginine test for diagnosis of adult GH deficiency. Link.