Sermorelin Was Approved Twice, and Withdrawn for Reasons That Had Nothing to Do With Whether It Worked

The molecule, and the two it gets confused with

Growth hormone releasing hormone runs to 44 amino acid residues, and sermorelin is residues 1 through 29 of it, amide capped at the tail, with nothing substituted along the chain. It raises plasma growth hormone by making the pituitary release the body's own.

Then the naming problem, which two other entries here run into. CJC-1295 is not sermorelin. The paper that named it describes a tetrasubstituted form of human GRF 1 to 29 with an added maleimidopropionamide derivative of lysine at the C terminus (PMID 15817669), four amino acids swapped out, at positions 2, 8, 15 and 27. Cut off the lysine extension that binds it to albumin and those four substitutions are still sitting there, and the result has its own name, modified GRF 1 to 29. So what the market sells as CJC-1295 without DAC is sermorelin with four amino acids changed rather than sermorelin itself. The tesamorelin entry counts sermorelin, CJC-1295 and modified GRF 1 to 29 as three analogues of one signal.

Approved twice, then withdrawn

Two approvals, two products, neither for an adult. NDA 19-863 covered Geref at 0.05 mg base per ampoule, approved 28 December 1990 for evaluating the pituitary somatotroph's ability to secrete growth hormone, a diagnostic test rather than a treatment. NDA 20-443 covered Geref at 0.5 mg and 1.0 mg base per vial, approved 26 September 1997 for idiopathic growth hormone deficiency in children with growth failure, at 30 mcg/kg nightly. EMD Serono held both.

Then the ending, in order, because the order is the argument. In a letter dated 11 July 2008, EMD Serono told FDA the 0.05 mg ampoule was being discontinued, and in a letter dated 2 December 2008 it said the same about the vials. In the Federal Register of 19 May 2009, at 74 FR 23407, FDA announced it was withdrawing approval of both applications, effective 18 June 2009, and no generic has appeared since. Then on 4 March 2013, at 78 FR 14095, FDA determined that neither had been withdrawn for reasons of safety or effectiveness.

That last sentence carries an industry. The determination came under 21 CFR 314.161, which governs generic applications, not compounding. Commentary ties sermorelin's continued availability from compounding pharmacies to it by way of section 503A, invoking two different conditions, one about being a component of an approved drug product, the other about staying off FDA's withdrawn-for-safety list. FDA has published no determination that sermorelin qualifies on either basis, and it is absent from the Federal Register notice of 1 May 2026 listing bulk substances with a clinical need under 503B, which I searched in full. It is on the 2026 World Anti-Doping Agency Prohibited List at S2.2.4, banned at all times.

What the trials in children found

Thorner and colleagues published the trial the 1997 approval rests on in JCEM in 1996: multicentre, open label, 110 previously untreated prepubertal children with growth hormone deficiency, 86 eligible for efficacy analysis, injecting 30 mcg/kg under the skin nightly for up to a year, height velocity going from 4.1 cm per year at baseline to 8.0 at six months and 7.2 at twelve (PMID 8772599). No control group, and deficient children grow when treated, so that is a response, not a margin.

The margin came from Chen 1993, which randomised 60 children whose deficiency came from the hypothalamus into three equal groups, the peptide at 30 or at 60 mcg/kg/day by continuous infusion, or growth hormone at 0.1 IU/kg/day, for six months. Mean height velocities were 9.2, 9.3 and 14.6 cm per year, growth hormone beating both peptide arms at p below 0.01 (PMID 8329830). Read the first two again. Doubling the dose moved height velocity by a tenth of a centimetre a year.

Neyzi 1993 ran the same comparison and did not get the same answer, which is the honest complication. Forty three prepubertal children were randomised to the peptide at 30 or 60 mcg/kg/day under the skin in three daily doses, or growth hormone at 0.1 IU/kg/day, for six months. Height velocity in the high dose peptide group came out comparable to the growth hormone group, and it was the bone age measure that separated them, rising only on growth hormone (PMID 8329826). Two trials, same year, same question, different routes and different splits.

What the adult record adds up to

Vittone and colleagues had 11 healthy non-obese men aged 64 to 76 with low baseline IGF-1 self-inject 2 mg under the skin nightly for six weeks (PMID 9005976). Nocturnal growth hormone release rose, and so did several strength measures. IGF-1 did not, and neither did weight, waist to hip ratio, DEXA muscle and fat, glucose or lipids. Six weeks, no control group, eleven men.

The trial people reach for instead is Khorram's, 19 subjects aged 55 to 71 on 10 mcg/kg under the skin nightly for 16 weeks, IGF-1 up and lean body mass up in the men only (PMID 9141536). It did not use sermorelin. It used the same 29 residues with norleucine in place of methionine at position 27, another molecule again. And the study quoted most often does not appear to exist: a 2021 Aging Cell trial said to have put 78 adults aged 55 to 70 on 200 mcg under the skin before bed for 24 weeks, for an 8.4 percent lean mass gain and a 6.2 percent visceral fat cut, carries no PMID and no authors, and I found no such paper.

What my own searching returned on 4 August 2026. PubMed gives 331 records for sermorelin and 29 filtered to clinical trials, none a randomised controlled trial of this peptide in healthy adults; the same search across its other names, limited to 2010 onward, returns 110 records, and adding the clinical trial filter returns zero. And I found no published trial giving it with ipamorelin, the pairing it is most often sold in.

Where 200 mcg came from

The convention that circulates is 200 to 300 mcg under the skin nightly at bedtime, titrated toward 500 mcg over roughly 16 weeks, often five nights on and two nights off. That is convention, not evidence.

The odd part is which direction it went. The pediatric label dose, 30 mcg/kg nightly, scales to roughly 2,100 mcg in a 70 kg adult, and the only published adult treatment study, Vittone 1997, used a flat 2 mg, or 2,000 mcg. Those two agree almost exactly, and the convention sits at about one seventh to one tenth of both. Grey market doses normally drift upward. This one drifted down, and I cannot choose between a deliberate scale-down for adults who are not deficient and a habit inherited from GHRP protocols. There is no approved adult labelling and no adult dose finding study.

What nobody has measured

Whether the anti-GRF antibodies matter in an adult. Thirty nine of the forty children on the two peptide arms of Chen's trial developed them, and nobody has looked in adults injecting nightly for months, the population using this now.

What the half life is. The label says 11 to 12 minutes whether given into a vein or under the skin and a 2026 review in Frontiers in Endocrinology tabulates about 4.3 minutes plus or minus 1.4 (PMID 42395176), and I could not locate the primary source behind the shorter figure.

My read

That same review grades sermorelin A*, the highest grade any growth hormone axis peptide gets in its table, against B for CJC-1295 with DAC and D for it without. Read the legend and the asterisk means historical regulatory approval with no current approval for performance or body composition indications. A grade earned by a pediatric approval that stopped existing in 2009 is doing work in sales copy for adult body recomposition.

Why Geref went away is in Chen's numbers rather than in any regulatory document. I found no FDA document stating why the manufacturer stopped, and it does not have to say. But a drug producing 9.2 cm per year against recombinant growth hormone's 14.6, same trial, same six months, was going to lose the only market it was approved for, and it had no adult market to fall back into. The commercial withdrawal is the most repeated fact about this compound, and it gets used to imply the drug was fine. It was fine. It also lost the head to head that used continuous infusion, and drew the one that injected under the skin, and neither of those trials was run in the adults now buying it.

If you have bought something labelled CJC-1295 without DAC, go and look at the certificate of analysis. Does it name an actual peptide, sermorelin or modified GRF 1 to 29, or does it hand the product name back to you?

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This content is for educational and informational purposes only and is not medical advice. Peptides discussed are research compounds and may not be approved for human use. Nothing here should be used to diagnose, treat, cure, or prevent any disease. Always consult a qualified healthcare professional before starting any peptide, supplement, or protocol. Individual responses vary. Do not self-administer compounds without proper medical supervision.