The class, defined
Growth hormone secretagogues are peptides that stimulate the body's own pituitary gland to release endogenous growth hormone, rather than replacing GH directly with recombinant human GH (somatropin). The class divides into two pharmacological families: GHRH analogs (sermorelin, CJC-1295, tesamorelin, mod GRF 1-29) that mimic hypothalamic growth-hormone-releasing hormone at the pituitary GHRH receptor, and ghrelin mimetics (ipamorelin, GHRP-2, GHRP-6, hexarelin, MK-677) that activate the growth-hormone secretagogue receptor (GHSR-1a). The two families are commonly stacked — GHRH analog plus ghrelin mimetic — because they produce synergistic GH release through independent pathways. Sermorelin is the original FDA-approved secretagogue (1997, withdrawn 2008 and subsequently available through compounding). Tesamorelin is FDA-approved for HIV-associated lipodystrophy. MK-677 is the only oral non-peptide compound. This hub catalogs the 11 GH secretagogues PeptaHub profiles, plus 6 related downstream anabolic peptides (IGF-1 analogs, MGF, follistatin) that are frequently used alongside the secretagogues in muscle-building protocols.
How they work
Growth hormone secretion is governed by the hypothalamic-pituitary axis: the hypothalamus releases GHRH (stimulatory) and somatostatin (inhibitory) into the portal circulation reaching the anterior pituitary, where somatotroph cells integrate the signals to release pulses of GH. A second stimulatory signal comes from the stomach: ghrelin, released during fasting, binds GHSR-1a on pituitary somatotrophs and synergizes with GHRH to amplify GH pulses. GH secretagogues split into GHRH analogs (acting at the GHRH receptor) and ghrelin mimetics (acting at GHSR-1a). Stacking one from each family produces additive or synergistic GH release because the two receptors converge on the same downstream signaling machinery but through independent agonist recognition.
GHRH analogs
Sermorelin is GHRH amino acids 1-29 — the minimum active fragment. Mod GRF 1-29 adds four amino-acid substitutions to extend serum stability. CJC-1295 without DAC is essentially Mod GRF 1-29. CJC-1295 with DAC adds a drug-affinity complex that binds albumin and extends half-life from minutes to days. Tesamorelin is a trans-3-hexenoyl-protected sermorelin-derivative developed for HIV lipodystrophy.
Ghrelin mimetics
Ipamorelin is a 5-amino-acid peptide — the first selective GHRP without cortisol, prolactin, or ACTH elevation. GHRP-2 and GHRP-6 are earlier-generation ghrelin mimetics with more off-target hormone elevation. Hexarelin is the most potent ghrelin mimetic but causes significant desensitization. MK-677 (ibutamoren) is an orally-bioavailable non-peptide ghrelin receptor agonist — the only oral option.
Stacking rationale
CJC-1295 + Ipamorelin is the most popular stack because (a) both are selective for GH without off-target hormone effects, (b) they combine a long-acting GHRH analog with a short-acting ghrelin mimetic for sustained baseline elevation plus pulse amplification, and (c) they have the cleanest side-effect profile. Other stacks (CJC-1295 + GHRP-2, hexarelin monotherapy) exist but are less favored.
Downstream anabolic signaling
GH stimulates hepatic IGF-1 production. IGF-1 mediates most of GH's anabolic effects on muscle, bone, and connective tissue. IGF-1 analogs (IGF-1 LR3, IGF-1 DES), MGF (mechano growth factor), PEG-MGF, and follistatin variants act downstream of GH to amplify muscle hypertrophy. They're listed in the 'Related anabolic peptides' section below because they are commonly stacked with GH secretagogues but are not themselves secretagogues.
The complete list
17 peptides, ordered by clinical evidence tier. Each entry links to the full profile with mechanism, dosing, side effects, and legal-status detail.
CJC-1295
Research (long-acting GHRH)Tetrasubstituted GHRH analog. With DAC (drug-affinity complex) extends half-life to ~8 days via albumin binding, producing sustained GH baseline elevation. Without DAC reverts to Mod GRF 1-29 with short half-life for pulse mimicry. The most popular GH secretagogue by volume.
Ipamorelin
Research (selective GHRP)Pentapeptide ghrelin mimetic — the first selective growth hormone secretagogue without cortisol, prolactin, or ACTH elevation. Stacks cleanly with CJC-1295 because the two target independent receptors without off-target hormone interference. The cleanest profile of any ghrelin mimetic.
Sermorelin
Previously FDA-approved; compoundingGHRH 1-29 — the minimum active fragment of endogenous GHRH. FDA-approved in 1997 as Geref for pediatric GH deficiency; discontinued commercially in 2008. Available via 503A compounding pharmacies in the US. Short half-life (~12 minutes) requires nightly dosing to mimic physiological GH pulses.
Tesamorelin
FDA-approved (Egrifta)Trans-3-hexenoyl-protected sermorelin-derivative approved for HIV-associated lipodystrophy (visceral fat reduction). The only GH secretagogue with current FDA approval for any indication. Sold as Egrifta. Also studied off-label for non-HIV visceral adiposity.
Hexarelin
Research (first-gen GHRP)Hexapeptide ghrelin mimetic. The most potent ghrelin-receptor agonist per dose but causes significant receptor desensitization with chronic use. Also elevates cortisol and prolactin more than ipamorelin. Used less frequently than selective ghrelin mimetics.
MK-677
Research (oral, non-peptide)Orally-bioavailable non-peptide ghrelin receptor agonist (spiropiperidine, not a peptide technically). Elevates GH and IGF-1 with once-daily dosing — the only oral option in this class. Side effects include fluid retention, insulin resistance, and appetite stimulation. Clinical development discontinued for frailty and osteoporosis.
GHRP-2
Research (ghrelin mimetic)Second-generation ghrelin mimetic with modestly better potency than GHRP-6 and less off-target cortisol/prolactin elevation. Still less selective than ipamorelin. Widely used in research protocols and older biohacker stacks.
GHRP-6
Research (ghrelin mimetic)Hexapeptide ghrelin mimetic with pronounced appetite stimulation — sometimes sought specifically for hunger amplification during bulking cycles. Elevates cortisol and prolactin more than second-gen agents. Largely displaced by ipamorelin and GHRP-2.
Mod GRF 1-29
Research (short-acting GHRH)Modified GHRH 1-29 with four amino-acid substitutions for improved serum stability. Essentially identical to CJC-1295 without DAC. Short half-life makes it suitable for pre-workout or pre-bed pulse stimulation.
GHRH
Research (endogenous reference)Endogenous hypothalamic growth-hormone-releasing hormone. The native peptide all GHRH analogs are engineered from. Used primarily as a reference compound and in diagnostic testing for GH deficiency.
Ghrelin
Research (endogenous ligand)Endogenous 28-amino-acid peptide released by the stomach. The natural ligand for GHSR-1a and the model molecule for every ghrelin-mimetic secretagogue. Appetite-stimulating and GH-releasing. Used primarily as a reference compound in research.
IGF-1 LR3
Related anabolic (downstream)Long-acting IGF-1 analog with arginine-3 substitution that extends half-life. Downstream mediator of GH's anabolic effects. Sometimes stacked with GH secretagogues for direct muscle hypertrophy. Not a secretagogue.
IGF-1 DES
Related anabolic (downstream)Truncated IGF-1 (des1-3) with reduced binding to IGFBPs and faster tissue clearance. Used for site-specific hypertrophy protocols. Downstream of GH, not a secretagogue.
MGF
Related anabolic (downstream)Mechano growth factor — a splice variant of IGF-1 produced by mechanically-stressed muscle fibers. Activates satellite cells for muscle repair and hypertrophy. Downstream of GH / IGF-1 signaling.
PEG-MGF
Related anabolic (downstream)Pegylated MGF with extended half-life for systemic dosing versus the local-action native form. Downstream of GH / IGF-1 signaling.
Follistatin-344
Related anabolic (myostatin inhibitor)344-amino-acid myostatin-binding peptide. Inhibits myostatin to remove the brake on muscle growth — a parallel pathway to GH / IGF-1 anabolism.
Follistatin-315
Related anabolic (myostatin inhibitor)Shorter 315-amino-acid follistatin isoform with different heparan-sulfate binding. Alternative myostatin inhibitor explored for muscle-wasting conditions.
Compared at a glance
Tesamorelin is the only GH secretagogue with current FDA approval; sermorelin was approved historically and remains available through 503A compounding. Everything else is research-only in the US regulatory sense, though several (CJC-1295, Ipamorelin, MK-677) have extensive clinical-trial data. The comparison table orders compounds by FDA status first, then by clinical development stage within unapproved compounds. The takeaway identifies the single most-popular stack and why.
| Peptide | Mechanism | Primary use | FDA status | Route | Half-life |
|---|---|---|---|---|---|
| Tesamorelin | GHRH analog (modified) | HIV lipodystrophy | Approved | SC daily | ~26 min |
| Sermorelin | GHRH 1-29 | GH deficiency | Compounding | SC nightly | ~12 min |
| CJC-1295 (w/DAC) | Long-acting GHRH | Body composition | Research | SC weekly | ~8 days |
| CJC-1295 (no DAC) | Short-acting GHRH | GH pulse | Research | SC | ~30 min |
| Ipamorelin | Selective GHRP | GH pulse | Research | SC | ~2 hours |
| MK-677 | Oral ghrelin agonist | Body composition | Research | Oral daily | ~4 hours |
| Hexarelin | Potent GHRP | GH pulse | Research | SC | ~55 min |
The CJC-1295 + Ipamorelin stack dominates this category because it pairs a long-acting GHRH analog with the cleanest selective ghrelin mimetic — no cortisol, prolactin, or ACTH elevation, and mechanistically additive GH release. For users seeking an FDA-approved option with the same outcome profile, tesamorelin (Egrifta) is the only approved path — but its approved indication is HIV lipodystrophy, so off-label use requires a prescriber willing to write for body composition.
Safety, side effects & legal status
GH secretagogues share a common side-effect profile tied to their mechanism: transient facial flushing and numbness after injection (common, benign, resolves within an hour), mild fluid retention, occasional morning fatigue during the first weeks of use, and dose-dependent insulin resistance with chronic stimulation. Long-term risks of elevating IGF-1 remain an unresolved concern — epidemiological data link higher IGF-1 levels to increased risks of colorectal, prostate, and breast cancer, but causation is unclear and the GH secretagogue trials have not been powered for oncologic endpoints. MK-677 has a distinctive side-effect profile including appetite stimulation, water retention, and dose-dependent impairment of insulin sensitivity that has halted its clinical development for several indications. All GH secretagogues are banned in competitive sports under WADA category S2 (growth factors / GH-releasing peptides). Tesamorelin is the only currently FDA-approved option; sermorelin is legally available through 503A compounding pharmacies when prescribed. Other compounds are research-only in the US regulatory sense, and their sale for human use is unauthorized.
How to think about this class
GH secretagogues have the most mature clinical-trial database of any research peptide class on PeptaHub outside of weight-loss peptides. CJC-1295 has been in human trials since 2004. Ipamorelin was the subject of a pivotal selectivity paper in 1998. Tesamorelin has FDA approval. Sermorelin has decades of pediatric-endocrinology use. Despite this, the off-label use of GH secretagogues for adult body composition and anti-aging remains outside evidence-based endocrinology practice — adult GH replacement is tightly indicated (documented GH deficiency on stimulation testing, pituitary disease, HIV lipodystrophy), and the longevity/body-composition case is weaker than its internet popularity suggests. Users considering GH secretagogues should work with a clinician who can interpret IGF-1 levels, monitor glucose tolerance, and weigh individual risk factors. The stack choice matters less than the decision about whether to use the class at all.
Frequently asked questions
A GH secretagogue is a compound that stimulates the pituitary gland to release the body's own growth hormone, as opposed to injecting recombinant human GH directly. The distinction matters for two reasons. First, secretagogues preserve the physiological pulsatility of GH release — normal GH secretion comes in short pulses, mostly during deep sleep, and secretagogues amplify these pulses rather than replacing them with a flat exogenous dose. Second, secretagogues rely on a functional pituitary. If the pituitary is damaged (e.g., after tumor or surgery), secretagogues won't work and exogenous GH is required. Most adults with low IGF-1 have functional pituitaries and can in principle respond to secretagogues.
CJC-1295 is a GHRH analog — it mimics the body's natural hypothalamic GHRH signal at the pituitary GHRH receptor. Ipamorelin is a ghrelin mimetic — it activates a different receptor (GHSR-1a) that also triggers GH release. The two pathways converge on the same somatotroph cells through independent agonist recognition, so stimulating both simultaneously produces additive or synergistic GH release. Stacking them is analogous to pressing two different buttons on the same machine. Additional reasons the stack dominates: ipamorelin is the most selective ghrelin mimetic (no cortisol, prolactin, or ACTH elevation), and CJC-1295 with DAC provides a sustained GHRH baseline that lasts days from a single injection.
Tesamorelin (brand name Egrifta) is the only currently FDA-approved GH secretagogue. Its approved indication is visceral fat reduction in HIV-associated lipodystrophy. Sermorelin was previously FDA-approved as Geref for pediatric growth hormone deficiency but was withdrawn commercially in 2008; it remains legally available through 503A compounding pharmacies when prescribed by a clinician. Everything else in this category — CJC-1295, Ipamorelin, GHRP-2, GHRP-6, Hexarelin, MK-677 — is classified as a research chemical in the US and is not legally sold for human use.
The evidence is more ambivalent than online enthusiasm suggests. Short-term trials (6–12 weeks) of CJC-1295 and related compounds show increased IGF-1 levels and modest improvements in body composition — usually a small reduction in body fat rather than a substantial increase in lean mass. Adult GH replacement trials (using recombinant GH directly) show similarly modest lean-mass effects, around 1–3% over 6 months. GH secretagogues work through GH, so their effects on muscle building are roughly constrained by what GH itself can do — which is less than the popular 'pro-bodybuilding' framing implies. For adults without documented GH deficiency, the lean-mass gains are typically modest compared with resistance training alone.
Yes. Every GH secretagogue — GHRH analogs, ghrelin mimetics, and downstream anabolic peptides like IGF-1 LR3 — is prohibited under WADA Category S2 (peptide hormones, growth factors, related substances and mimetics). The ban covers both competition and out-of-competition periods. Detection methods vary: some compounds are directly assayable in blood or urine, others are inferred via elevated IGF-1 or specific ratios. Athletes subject to WADA, USADA, NCAA, or professional sports drug-testing should assume all compounds in this pillar are prohibited and that sophisticated detection methods are actively in use.
The most common short-term effects are transient facial flushing, injection-site reactions, mild fluid retention, and occasional morning fatigue during the first weeks. Dose-dependent insulin resistance develops with chronic use — monitoring fasting glucose and HbA1c is advisable during extended protocols. The unresolved long-term concern is IGF-1 elevation and its epidemiological association with increased risks of several cancers (colorectal, prostate, breast). Causation remains unproven and the cancer association may reflect endogenous high-IGF-1 states rather than exogenous stimulation, but the uncertainty is meaningful enough that clinicians who prescribe GH secretagogues typically screen for oncologic risk factors and monitor IGF-1 levels during treatment.
MK-677 is the only orally-bioavailable compound in this class and achieves comparable IGF-1 elevation to injectable ghrelin mimetics on a mg-for-mg basis. Convenience is its main advantage over CJC-1295 + Ipamorelin — one pill a day versus subcutaneous injections. The downsides are a more pronounced appetite-stimulation effect, more water retention, and more impairment of insulin sensitivity at effective doses compared with ipamorelin. Clinical development of MK-677 was discontinued for frailty and osteoporosis indications partly because of the insulin-resistance side-effect profile. Users wanting oral dosing accept a worse side-effect profile in exchange for convenience.
Sources & further reading
External citations underpinning this page. PeptaHub's full sourcing methodology is documented at /methodology — every claim on this page traces back to one of these references or a linked profile.
- Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295 (Teichman et al.) — PubMed
- Ipamorelin, the first selective growth hormone secretagogue (Raun et al.) — PubMed
- Tesamorelin (Egrifta) drug label — FDA
- Peptides for Bodybuilding — category context — Healthline
- Prohibited List — WADA
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