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Comparisons15 min read

CJC-1295 vs. Sermorelin: Growth Hormone Peptides

CJC-1295 and sermorelin share a common ancestor — human growth hormone-releasing hormone (GHRH) — but they are not the same molecule, and they do not behave the same way in the body. Sermorelin is, structurally, a faithful copy of the first 29 amino acids of natural GHRH.

CJC-1295 and sermorelin share a common ancestor — human growth hormone-releasing hormone (GHRH) — but they are not the same molecule, and they do not behave the same way in the body. Sermorelin is, structurally, a faithful copy of the first 29 amino acids of natural GHRH. CJC-1295 starts from that same template but rewrites it: four amino acid substitutions and, in the DAC version, a chemical tether to blood proteins that keeps the peptide circulating for days instead of minutes.

That difference sounds technical. In practice, it changes everything: how often each peptide needs to be administered, how growth hormone levels rise and fall after a dose, how the pituitary responds over time, and what the regulatory picture looks like for each compound. Sermorelin once had full FDA approval. CJC-1295 never got past Phase II trials.

This guide breaks down the pharmacology, clinical evidence, and practical differences.

Table of Contents

Head-to-Head Comparison

FeatureSermorelinCJC-1295 (without DAC)CJC-1295 (with DAC)
Chemical IdentityGHRH(1-29)NH₂Modified GRF(1-29), tetrasubstitutedModified GRF(1-29) + Drug Affinity Complex
Amino Acids293030 + lysine-MPA linker
Molecular Weight~3,358 Da~3,367 Da~3,647 Da
Half-Life10–12 minutes30 minutes to ~2 hours6–8 days
Dosing FrequencyDaily (typically at bedtime)1–3 times daily or combined with GHRP1–2 times per week
GH Release PatternPulsatile, physiologicPulsatile, slightly extendedElevated trough with preserved pulsatility
Peak GH Increase2–5 fold above baselineComparable to sermorelin per dose2–10 fold, sustained for 6+ days
IGF-1 ElevationModerate, returns to baseline within hoursModerate, slightly prolonged1.5–3 fold for 9–11 days
FDA ApprovalApproved 1997, withdrawn 2008 (not safety-related)Never approvedNever approved
Compounding Status (U.S.)Legal under 503ACurrently restrictedCurrently restricted
Key Clinical StudyKhorram et al. 1997; Vittone et al.Teichman et al. 2006Teichman et al. 2006; Ionescu et al. 2006

What Is Sermorelin?

Sermorelin (brand names: Geref, Geref Diagnostic) is a synthetic peptide made up of the first 29 amino acids of human GHRH. Full-length GHRH contains 44 amino acids, but researchers established in the 1980s that the first 29 residues carry the full biological punch — sermorelin and native GHRH have equivalent potency at the GHRH receptor (DrugBank).

The FDA approved sermorelin acetate for intravenous injection as a diagnostic tool in 1990, then approved subcutaneous formulations in 1997 for treating children with idiopathic growth hormone deficiency. For nearly a decade, it was a mainstream pharmaceutical product prescribed by endocrinologists.

In 2008, EMD Serono — the company marketing Geref — discontinued it. The reason had nothing to do with safety or efficacy. Manufacturing difficulties and commercial considerations drove the decision (PMC2699646). Today, sermorelin remains available through compounding pharmacies under Section 503A of the Federal Food, Drug, and Cosmetic Act. It has an established USP monograph, a fact that sets it apart from most other peptides used in anti-aging and optimization contexts.

What Is CJC-1295?

CJC-1295 was developed in the early 2000s by ConjuChem Biotechnologies, a Montreal-based company, with a specific goal: fix what was wrong with sermorelin. The problem wasn't receptor binding or GH stimulation — sermorelin did both just fine. The problem was survival time in the bloodstream.

Native GHRH (and by extension, sermorelin) is chewed up by the enzyme dipeptidyl peptidase-4 (DPP-IV) within minutes of injection. CJC-1295 addresses this through four targeted amino acid substitutions at positions 2, 8, 15, and 27:

  • Position 2: L-alanine replaced with D-alanine (resists DPP-IV cleavage)
  • Position 8: Asparagine swapped for glutamine (reduces deamidation)
  • Position 15: Glycine replaced with alanine (improves receptor binding stability)
  • Position 27: Methionine replaced with leucine (prevents oxidative degradation)

These changes extend the half-life of CJC-1295 without DAC (also called Modified GRF 1-29) from roughly 10 minutes to about 30 minutes — a useful improvement, but not a game-changer.

The real leap came with CJC-1295 with DAC. ConjuChem added a Drug Affinity Complex: a lysine residue linked to maleimidoproprionic acid (MPA) at the C-terminus. After injection, this reactive group forms a covalent bond with circulating albumin, essentially hitching a ride on the body's most abundant blood protein. The result is a half-life of 6 to 8 days in humans — roughly 700 times longer than native GHRH (Teichman et al., 2006).

CJC-1295 reached Phase II clinical trials for growth hormone deficiency and lipodystrophy, but development was halted after a participant death during the trial. The attending physician attributed the death to asymptomatic coronary artery disease unrelated to the drug, but the program was not resumed. CJC-1295 has never been FDA-approved (Wikipedia).

Mechanism of Action: Same Target, Different Approaches

Both sermorelin and CJC-1295 act on the same receptor: the growth hormone-releasing hormone receptor (GHRHR) on somatotroph cells in the anterior pituitary gland. When either peptide binds GHRHR, the receptor activates a Gs protein, which in turn stimulates adenylyl cyclase, raises intracellular cyclic AMP (cAMP), and activates protein kinase A (PKA). This signaling cascade promotes GH gene transcription, GH protein synthesis, and GH release into the bloodstream.

Because both peptides stimulate endogenous GH production rather than supplying exogenous growth hormone, the pituitary's built-in regulatory system remains intact. Somatostatin — the hypothalamic brake on GH release — still functions normally, creating a ceiling on how much GH can be released. This is a meaningful safety advantage over recombinant human growth hormone (rhGH), where an external dose bypasses these controls and can push GH to supraphysiologic levels (Walker, 2006).

The downstream effect of both peptides: elevated GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1), the mediator responsible for many of growth hormone's anabolic, metabolic, and regenerative effects.

So what's different? The mechanism itself is essentially identical. Both peptides activate the same receptor and trigger the same signaling pathway. The difference lies entirely in pharmacokinetics — how long each peptide survives in circulation and, consequently, the pattern of GH stimulation it produces.

Pharmacokinetics: Where the Real Differences Live

Sermorelin: Fast In, Fast Out

After subcutaneous injection of 2 mg sermorelin, plasma concentrations peak within 5–20 minutes. Clearance is rapid: 2.4–2.8 L/min in adults. The plasma half-life clocks in at 10–12 minutes regardless of whether you're measuring IV or subcutaneous routes (ScienceDirect).

Despite disappearing from the blood within the hour, sermorelin's pharmacodynamic effect (the actual GH release it triggers) lasts longer — roughly 1 to 3 hours. Transient receptor occupancy is enough to set off the intracellular signaling cascade that results in a GH pulse. This creates a pattern that closely mirrors the body's natural nocturnal GH secretion, especially when administered at bedtime.

CJC-1295 without DAC: The Middle Ground

Modified GRF 1-29 — CJC-1295 without the albumin-binding component — has a half-life of approximately 30 minutes to 2 hours. The four amino acid substitutions slow proteolytic degradation enough to produce a slightly longer window of GHRH receptor stimulation than sermorelin. In practice, it is frequently dosed 1–3 times daily and often combined with a growth hormone-releasing peptide (GHRP) like ipamorelin to amplify each pulse.

CJC-1295 with DAC: Sustained Elevation

The DAC version changes the game entirely. A single subcutaneous injection of CJC-1295 DAC at 60 mcg/kg produced a roughly 150% increase in mean GH levels sustained over 6 or more days. At 250 mcg/kg (a high research dose, not a typical clinical dose), GH area under the curve (AUC) increased more than 300%. IGF-1 levels rose 1.5- to 3-fold and stayed elevated for 9–11 days. After repeated weekly dosing, mean IGF-1 remained above baseline for up to 28 days — evidence of a cumulative pharmacokinetic effect (Teichman et al., 2006).

A companion study by Ionescu and Bhatt (2006) confirmed that GH pulsatility was preserved under continuous CJC-1295 stimulation — the pituitary didn't flatline into a steady-state output. Pulse frequency and amplitude remained intact, but basal (trough) GH levels rose 7.5-fold, and mean overall GH secretion increased 46% (Ionescu et al., 2006). IGF-1 rose 45%.

This pharmacokinetic profile means fewer injections (once or twice per week) but a fundamentally different pattern of GH exposure compared to sermorelin's brief, bedtime-driven pulses.

Clinical Evidence: What the Studies Actually Show

Sermorelin Clinical Data

Sermorelin benefits from a longer history of human clinical research. Key studies include:

Khorram et al. (1997) — A single-blind, placebo-controlled trial studied 19 adults aged 55–71 who self-injected sermorelin (10 mcg/kg) nightly for 16 weeks. Nocturnal GH and serum IGF-1 levels increased significantly in both men and women. Men saw a 1.26 kg increase in lean body mass, improved insulin sensitivity, and reported better libido and quality of life. Skin thickness increased in both sexes (PubMed 9141536).

Vittone et al. — Eleven men aged 64–76 received 2 mg sermorelin nightly for six weeks. The 12-hour mean GH release nearly doubled, but peak amplitude and pulse number stayed unchanged. Sermorelin augmented the duration of rhythmic GH release without pushing levels above physiologic norms.

Corpas et al. (1992) — Demonstrated that short-term GHRH administration could reverse age-related reductions in GH and IGF-1 in older men, with IGF-1 levels approaching those seen in younger adults.

Walker (2006) — Argued in Clinical Interventions in Aging that sermorelin's ability to restore pituitary function ("pituitary recrudescence") makes it better suited for aging adults than recombinant GH, because it preserves the entire hypothalamic-pituitary feedback loop rather than replacing it.

CJC-1295 Clinical Data

CJC-1295's clinical evidence is narrower — concentrated largely in two trials conducted by ConjuChem:

Teichman et al. (2006) — Published in the Journal of Clinical Endocrinology & Metabolism, this landmark study included two randomized, placebo-controlled, double-blind, ascending-dose trials in healthy subjects aged 21–61, running 28 and 49 days. A single injection produced dose-dependent GH increases (2- to 10-fold) sustained for 6+ days and IGF-1 increases (1.5- to 3-fold) for 9–11 days. Multiple doses showed cumulative effects, with IGF-1 remaining elevated for up to 28 days. The peptide was "safe and relatively well tolerated, particularly at doses of 30 or 60 mcg/kg" (JCEM).

Ionescu and Bhatt (2006) — Confirmed preserved GH pulsatility under continuous CJC-1295 stimulation, with 7.5-fold increases in trough GH and 45% increases in IGF-1 (PubMed 17018654).

Sackmann-Sala et al. (2009) — A proteomic follow-up found significant increases in GH and IGF-1 one week post-CJC-1295 administration, along with changes in serum protein profiles that may represent biomarkers of GH/IGF-1 action (PMC2787983).

No large-scale trials examining CJC-1295's effects on body composition, muscle mass, fat loss, or functional outcomes in adults were completed before the program was discontinued.

Safety and Side Effects

Sermorelin

Sermorelin's safety profile is well-established from its years as an FDA-approved drug. In clinical trials involving 350 patients:

  • Most common side effect: Injection site reactions (pain, swelling, redness) — about 1 in 6 patients
  • Rare side effects (under 1%): Headache, flushing, difficulty swallowing, dizziness, hyperactivity, drowsiness, hives
  • Only 3 of 350 patients discontinued therapy due to injection reactions
  • Thyroid monitoring required: Hypothyroidism occurred in 6.5% of patients during sermorelin therapy. Untreated hypothyroidism can blunt GH response, so thyroid hormone levels should be checked before and during treatment (RxList)

Because sermorelin works through the body's natural feedback loop (somatostatin still puts the brakes on GH release), the risk of GH overproduction is inherently low. You can't easily "overdose" on sermorelin the way you can with direct rhGH injections.

CJC-1295

CJC-1295's safety data comes from a smaller pool of clinical trial participants. At doses of 30 and 60 mcg/kg, side effects were generally mild:

  • Injection site reactions
  • Transient flushing and warmth (vasodilatory effect)
  • Headache
  • The FDA has flagged cardiovascular concerns including increased heart rate and transient hypotension

The more significant safety concern was the death of a trial participant during Phase II studies. Investigators attributed it to pre-existing coronary artery disease rather than the drug, but the incident halted the clinical program. In July 2025, the FDA issued a Class II recall for a compounded CJC-1295 injectable due to sterility concerns — a reminder that quality control matters enormously with compounded peptides.

Because CJC-1295 DAC keeps GH elevated for days rather than hours, the theoretical risk of prolonged hyperglycemia, fluid retention, or other GH-related side effects is higher than with sermorelin's brief pulses.

This is where the two peptides diverge most sharply in practical terms.

Sermorelin was FDA-approved in 1997 and withdrawn in 2008 purely for commercial and manufacturing reasons. It has an established United States Pharmacopeia (USP) monograph. Under current regulations, sermorelin can be legally compounded by 503A pharmacies with a valid prescription. Of the two peptides, sermorelin is far easier to access legally in the United States.

CJC-1295 has never been FDA-approved. In September 2024, the FDA removed CJC-1295 (along with ipamorelin, BPC-157, and several other peptides) from its Category 2 list — but this did not clear it for compounding. The nominators had withdrawn their nominations, shifting the substances into a new review process through the Pharmacy Compounding Advisory Committee (PCAC). As of early 2026, the FDA has recommended against including CJC-1295 in the 503A bulks regulation, effectively keeping it off-limits for compounding pharmacies.

For a deeper look at the regulatory differences between stimulating your own GH versus replacing it directly, see our comparison of peptide therapy vs. HGH therapy.

Combination Strategies: Stacking with Ipamorelin

Both sermorelin and CJC-1295 are GHRH analogs — they amplify the GH release signal. Growth hormone-releasing peptides (GHRPs) like ipamorelin work through a completely different receptor (the ghrelin receptor, GHS-R1a) and a different signaling pathway (calcium-dependent rather than cAMP-dependent). Combining a GHRH analog with a GHRP creates a dual-receptor stimulation that can produce 3- to 5-fold greater GH release than either peptide alone, according to preclinical data and clinical observation.

CJC-1295 + Ipamorelin is the more widely discussed combination. The rationale: CJC-1295 (without DAC) provides the GHRH "amplifier" signal while ipamorelin provides the "initiator" pulse. For a detailed guide on this combination, see How to Stack CJC-1295 and Ipamorelin.

Sermorelin + Ipamorelin follows the same pharmacological logic but with sermorelin's shorter half-life. Some clinicians prefer this combination for patients who want a more conservative approach with a peptide that has a stronger regulatory pedigree.

No large-scale randomized controlled trial has studied either combination for body composition or performance outcomes. The "synergy" is supported by mechanistic reasoning and receptor pharmacology, but translational evidence remains limited. For a broader look at secretagogue options, see MK-677 vs. CJC-1295/Ipamorelin.

When Clinicians Choose One Over the Other

The choice between sermorelin and CJC-1295 hinges on several factors:

Reasons to favor sermorelin:

  • Regulatory safety net. Sermorelin was FDA-approved, has a USP monograph, and can be legally compounded. For clinicians and patients who prioritize working within the regulatory framework, this matters.
  • Physiologic GH pattern. Sermorelin's short half-life produces a GH pulse that closely mirrors the body's natural nocturnal secretion. If the clinical goal is to restore youthful GH dynamics — not to blast GH levels as high as possible — sermorelin fits the philosophy.
  • Lower risk of prolonged side effects. A 10-minute half-life means any adverse effect wears off quickly. With CJC-1295 DAC, an unwanted response can persist for days.
  • More extensive clinical data. Multiple clinical trials in both children and adults, plus years of post-market use, give sermorelin a deeper safety record.

Reasons to favor CJC-1295:

  • Convenience. CJC-1295 with DAC requires only one to two injections per week versus daily injections for sermorelin. Adherence tends to be higher with less frequent dosing.
  • Stronger GH/IGF-1 response. The pharmacokinetic data is clear: CJC-1295 produces larger, longer-lasting elevations in GH and IGF-1 than sermorelin, dose for dose.
  • Cumulative effect. Weekly dosing of CJC-1295 DAC builds on itself — IGF-1 levels continued to rise over 28 days of repeated dosing in the Teichman trial, suggesting progressive pituitary activation.
  • Combination potential. CJC-1295 (without DAC) paired with ipamorelin is one of the most extensively discussed secretagogue combinations in the peptide therapy space.

For a related comparison involving another GHRH analog, see our guide on sermorelin vs. tesamorelin. Tesamorelin is the only GHRH analog that currently holds active FDA approval (for HIV-associated lipodystrophy), making it another important point of reference.

Frequently Asked Questions

Are CJC-1295 and sermorelin the same thing?

No. Sermorelin is a direct copy of the first 29 amino acids of natural GHRH. CJC-1295 starts from the same sequence but includes four amino acid substitutions designed to resist enzymatic degradation, plus (in the DAC version) a chemical linker that binds to albumin. They target the same receptor but have dramatically different half-lives and dosing requirements.

Which produces a stronger growth hormone response?

CJC-1295, particularly with DAC. In clinical trials, a single injection of CJC-1295 at 60 mcg/kg increased mean GH levels roughly 150%. At higher doses, GH AUC rose over 300%. Sermorelin produces meaningful GH pulses, but they are shorter-lived and smaller in magnitude.

Is sermorelin safer than CJC-1295?

Sermorelin has a more established safety profile — FDA-approved, studied in hundreds of patients, and years of post-market use. CJC-1295's safety data comes from fewer trial participants. Sermorelin's short half-life also means any side effects resolve quickly, while CJC-1295 DAC's effects persist for days.

Can you take sermorelin and CJC-1295 together?

This is not a standard protocol. Since both peptides act on the same GHRH receptor, combining them provides little pharmacological advantage. Clinicians typically choose one GHRH analog and, if desired, pair it with a GHRP like ipamorelin that works through a different receptor pathway.

Sermorelin can be legally compounded under 503A with a prescription. CJC-1295 is not currently cleared for compounding under FDA regulations as of early 2026, though its regulatory status remains subject to change.

What about CJC-1295 without DAC versus sermorelin?

CJC-1295 without DAC (Modified GRF 1-29) has a half-life of roughly 30 minutes — longer than sermorelin's 10–12 minutes but far shorter than the DAC version's 6–8 days. It represents a middle ground and is typically dosed alongside a GHRP, still requiring multiple daily injections.

The Bottom Line

Sermorelin and CJC-1295 are both GHRH analogs that stimulate the pituitary to release growth hormone through the same receptor and signaling pathway. They diverge in half-life, dosing convenience, regulatory status, and the depth of their clinical evidence.

Sermorelin is the proven original — shorter-acting, requiring daily injections, but backed by FDA approval history, an established safety record, and legal accessibility through compounding. CJC-1295, particularly with DAC, is the pharmacokinetically engineered successor — longer-acting, more convenient, capable of producing larger and more sustained GH elevations, but lacking FDA approval and currently restricted from compounding.

Neither peptide has been proven in large-scale trials to improve body composition, slow aging, or boost athletic performance. Both increase GH and IGF-1 levels in clinical settings. Whether those hormonal changes translate into meaningful, measurable health outcomes depends on factors that the existing research has not fully answered.

What the data does support: both peptides stimulate endogenous GH through physiologic mechanisms, and both preserve natural feedback controls. The choice comes down to risk tolerance, legal access, dosing preference, and how aggressively one wants to raise growth hormone levels — always under medical supervision.

References

  1. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Bhatt R. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PubMed

  2. Ionescu M, Bhatt R. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PubMed

  3. Sackmann-Sala L, Ding J, Frohman LA, Bhatt R. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res. 2009;19(6):471-477. PMC

  4. Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging. 2006;1(4):307-308. PMC

  5. 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. PubMed

  6. Ishida J, Saitoh M, Ebner N, Springer J, Anker SD, von Haehling S. Growth hormone secretagogues: history, mechanism of action, and clinical development. JCSM Rapid Commun. 2020;3(1):25-37. Wiley

  7. Sermorelin acetate. DrugBank. DrugBank DB00010

  8. CJC-1295. Wikipedia. Wikipedia

  9. Sigalos JT, Pastuszak AW. The role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020;9(Suppl 2):S149-S159. PMC