Growth hormone secretagogues are compounds that prompt your pituitary gland to release more of your own growth hormone (GH), instead of supplying GH directly. The category includes an FDA-approved drug, a formerly approved drug, and a long list of research compounds. Here’s how they work and how they compare.
Key takeaways
- Secretagogues work through two main pathways: GHRH receptors and ghrelin receptors.
- Tesamorelin (Egrifta) is FDA-approved for a specific condition in people with HIV.
- Sermorelin was FDA-approved in the past; the brand was discontinued in 2008.
- Ipamorelin, GHRP-2, GHRP-6, CJC-1295 and MK-677 are not FDA-approved.
How the growth hormone system works
GH release is controlled by a push-and-pull system:
- GHRH (growth hormone–releasing hormone) from the hypothalamus pushes GH release.
- Somatostatin puts the brakes on.
- Ghrelin, the “hunger hormone,” also stimulates GH release through its own receptor.
- GH signals the liver to make IGF-1, which feeds back to slow further release.
Because the body’s feedback loops stay in place, secretagogues are thought to produce a more regulated GH rise than injecting GH itself. That’s the theory; long-term comparisons are limited.
Pathway 1: GHRH analogs
Tesamorelin
Tesamorelin is a stabilized version of full-length GHRH. The FDA approved it as Egrifta in 2010 to reduce excess abdominal fat in adults with HIV who have lipodystrophy. It is not approved for general weight loss or anti-aging. Its dose depends on which formulation is prescribed, so follow the current prescribing information.
Sermorelin
Sermorelin is GRF (1-29), the shortest fully active piece of GHRH. It was approved as Geref for evaluating and treating GH deficiency in children. The maker discontinued it in 2008 for business and manufacturing reasons rather than safety. It remains available in some places through compounding.
CJC-1295
A modified GRF (1-29), with or without an albumin-binding DAC group. Never approved. See CJC-1295 with DAC vs without DAC.
Pathway 2: ghrelin mimetics (GHRPs)
Ipamorelin
Developed in the late 1990s, ipamorelin was described in early research as more selective than older GHRPs, raising GH with little effect on cortisol or prolactin in animal studies. It has been tested in human trials for other purposes (such as bowel recovery after surgery) but is not approved for any use.
GHRP-2 and GHRP-6
Older synthetic GH-releasing peptides. GHRP-6 is known for strongly increasing hunger, consistent with ghrelin-receptor activity. GHRP-2 is more potent for GH but can also raise cortisol and prolactin. Neither is FDA-approved.
MK-677 (ibutamoren)
Not a peptide at all. It’s an oral small molecule that activates the ghrelin receptor. Studies in adults showed it raises GH and IGF-1 over time, along with increased appetite, fluid retention and reduced insulin sensitivity. Not FDA-approved.
Comparison table
| Compound | Pathway | Form | FDA status |
|---|---|---|---|
| Tesamorelin | GHRH | Injection | Approved (Egrifta), specific indication |
| Sermorelin | GHRH | Injection | Previously approved; brand discontinued |
| CJC-1295 | GHRH | Injection | Not approved |
| Ipamorelin | Ghrelin | Injection | Not approved |
| GHRP-2 / GHRP-6 | Ghrelin | Injection | Not approved |
| MK-677 | Ghrelin | Oral (small molecule) | Not approved |
Why the two pathways get combined
GHRH analogs and ghrelin mimetics act on different receptors. Physiology research shows that stimulating both at once produces a larger GH release than either alone. That’s the logic behind pairings like CJC-1295 with ipamorelin. Controlled long-term human data on these combinations doesn’t exist.
Side effects and risks
- Injection-site reactions, flushing and headache
- Fluid retention, joint aches, and numbness or tingling in the hands
- Increased hunger (especially GHRP-6 and MK-677)
- Reduced insulin sensitivity and higher blood sugar
- Unknown long-term effects of sustained higher IGF-1, including on existing tumors
Tesamorelin’s label lists its own warnings and contraindications, including pregnancy and disruption of the hypothalamic-pituitary axis.
Sports and drug testing
All of these compounds, including MK-677, are prohibited by WADA under the S2 category. See Peptides and sports drug testing.
Dosing
Only tesamorelin has a current FDA label with a dose, and it’s formulation-specific. The other compounds here have no established human dose, so Pep Guide doesn’t list one.
Frequently asked questions
What is a growth hormone secretagogue?
A compound that causes the pituitary gland to release more of the body’s own growth hormone, usually by acting on GHRH receptors or ghrelin receptors.
Is sermorelin FDA-approved?
Sermorelin was approved as Geref, but the brand was discontinued in 2008 for business reasons. It is not currently marketed as an approved brand in the US.
Is MK-677 a peptide?
No. MK-677 (ibutamoren) is an oral small molecule that activates the ghrelin receptor. It is often grouped with peptides because it has a similar effect.
Are growth hormone secretagogues safer than HGH?
They are thought to keep more of the body’s natural feedback in place, but there are few long-term human studies comparing them directly with growth hormone.
Medical disclaimer: Pep Guide is for educational purposes only. It is not medical advice, diagnosis or treatment. Research changes over time. Talk to a licensed healthcare provider before starting, stopping or changing any medication or compound.