Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

Growth hormone secretagogues (GHRH and ghrelin mimetics): glucose, fluid retention and IGF-1 risks

A class-wide safety review of CJC-1295, ipamorelin, sermorelin, tesamorelin, GHRP-2, GHRP-6, hexarelin and MK-677

Evidence verdict: Moderate for the class signals where they come from an FDA label (tesamorelin) or RCTs (MK-677). Very limited or absent for most gray-market secretagogues, which have no long-term human safety data. [2, 1, 4]

Last reviewed: Oct 27, 2026

In 30 seconds

• Raising growth hormone (GH) and IGF-1 tends to raise blood sugar and lower insulin sensitivity. In a 2-year RCT in older adults, MK-677 raised fasting glucose and lowered insulin sensitivity. [1] [Controlled study]
• The tesamorelin label warns of glucose intolerance or diabetes, fluid retention (swelling, joint pain, carpal tunnel syndrome) and IGF-1 elevation, and contraindicates it in active cancer and pregnancy. [2] [Regulatory]
• An MK-677 trial in older hip-fracture patients was stopped early for a congestive heart failure safety signal. [3] [Controlled study]
• Most secretagogues sold online (CJC-1295, ipamorelin, GHRP-2, GHRP-6, hexarelin) are not FDA-approved, are banned in sport, and have only short, small human studies. [4, 5] [Review, Regulatory]

Why the class shares risks

These compounds act upstream of GH. GHRH analogs (sermorelin, tesamorelin, CJC-1295) stimulate the GHRH receptor, and ghrelin mimetics (GHRP-2, GHRP-6, hexarelin, ipamorelin, MK-677) stimulate the ghrelin (GH-secretagogue) receptor. Either way, GH and then IGF-1 rise. [6, 1, 4] [Controlled study, Review] GH itself counters insulin and causes fluid retention, which is why the somatropin label lists fluid retention (swelling, joint pain, carpal tunnel syndrome) and contraindicates active malignancy. [7] [Regulatory] A 2026 review of performance-oriented GH-axis peptides lists prolactin and cortisol rises, appetite changes, dysglycemia, fluid retention, muscle and joint pain, and injection-site reactions as reported harms. [4] [Review]

Glucose and insulin sensitivity

• MK-677 (ibutamoren): in 65 healthy adults aged 60–81 over 2 years, it raised GH and IGF-1 to young-adult levels and increased fat-free mass, but fasting glucose rose by about 0.3 mmol/L and insulin sensitivity fell. Appetite increase, mild leg swelling and muscle pain were the most frequent side effects, and cortisol rose. Strength and function did not improve. [1] [Controlled study]
• Tesamorelin (Egrifta SV): the label reports HbA1c of 6.5% or higher at week 26 in 5% of tesamorelin versus 1% of placebo patients, and an increased risk of developing diabetes. It advises checking glucose before and during treatment. [2] [Regulatory] The pivotal NEJM trial found no significant difference in glycemic measures over 26 weeks. [8] [Controlled study]
• Other secretagogues: no long-term glucose data were found for CJC-1295, ipamorelin, GHRP-2, GHRP-6 or hexarelin. UNVERIFIED

Fluid retention, carpal tunnel and heart failure

The tesamorelin label lists fluid retention, including edema, joint pain and carpal tunnel syndrome. [2] [Regulatory] In MK-677 users, transient mild lower-leg swelling was common. [1] In a phase IIb trial of 123 older adults recovering from hip fracture, MK-677 raised IGF-1 but did not improve most function measures. The trial was terminated early because of a congestive heart failure signal in a limited number of patients, and the authors called the safety profile unfavorable in that population. [3] [Controlled study]

IGF-1 and cancer

Higher circulating IGF-1 is associated with modestly higher risk of some cancers. A meta-analysis linked high IGF-1 to prostate and premenopausal breast cancer, but the associations were modest and varied by site. [9] [Observational] That observational link does not prove that raising IGF-1 causes cancer. Regulators still treat it as a real concern: tesamorelin and somatropin are contraindicated in active malignancy, and the tesamorelin label advises monitoring IGF-1 and considering stopping if it stays elevated. [2, 7] [Regulatory] No cancer-outcome data exist for unapproved secretagogues. UNVERIFIED

Other hormones and tolerance

GHRP-2 and hexarelin are not fully GH-specific: in healthy adults they also raised prolactin, ACTH and cortisol. [10] [Controlled study] Daily GHRP-2 for 5 days showed a shrinking GH response and no rise in IGF-1. [11] [Controlled study] Ipamorelin was well tolerated in a 114-patient postoperative-ileus trial but did not beat placebo on efficacy. [12] [Controlled study] CJC-1295 raised GH and IGF-1 for days after a single injection in short trials, with no serious adverse reactions reported, but long-term safety was never established. [6] [Controlled study]

Regulatory and sport status

Tesamorelin (Egrifta SV) is FDA-approved for a specific HIV-related indication. [2] CJC-1295, ipamorelin, GHRP-2, GHRP-6, hexarelin and MK-677 are not FDA-approved drugs. Ipamorelin is on FDA's compounding safety-risk list. [13] [Regulatory] WADA prohibits GHRH analogs, GH secretagogues and GHRPs at all times under S2. [5] [Regulatory] This page gives no dosing or cycling information. See the individual compound pages for study details.

Evidence levels used on this page

• [Regulatory] FDA, USP or WADA primary document or an FDA-approved label. [Controlled study] randomized trial or systematic review of trials. [Observational] surveillance, pharmacovigilance or cohort data. [Lab] analytical, cell or animal work. [Guidance] professional-society guidance. [Policy] Open Peptide Project published policy.

Related

MK-677, Tesamorelin, CJC-1295, Ipamorelin, Sermorelin, GHRP-2, GHRP-6, Hexarelin

References

1. Nass R, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008. PMID 18981485.
2. EGRIFTA SV (tesamorelin) prescribing information, Theratechnologies (BLA 022505). setid 3d783378-b02d-4f19-99dd-0fc91a042224, effective Jul 29, 2026.
3. Adunsky A, et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011. PMID 21067829.
4. Dominikowski et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration. Front Endocrinol (Lausanne). 2026. PMID 42395176.
5. World Anti-Doping Agency. 2026 Prohibited List (in force 1 January 2026), section S2. https://www.wada-ama.org/en/prohibited-list
6. Teichman SL, et al. 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. PMID 16352683.
7. GENOTROPIN (somatropin) prescribing information, Pfizer (BLA 020280). setid ffebf88b-d257-4542-9808-74d9b7167765, effective Aug 4, 2026.
8. Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007. PMID 18057338.
9. Renehan AG, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004. PMID 15110491.
10. Arvat E, et al. Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Peptides. 1997. PMID 9285939.
11. Nijland EA, et al. A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men. Eur J Endocrinol. 1998. PMID 9820615.
12. Beck DE, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis. 2014. PMID 25331030.
13. US FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (content current as of 04/22/2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks

Disclaimer: This page is for education only. It is not medical advice, and it does not endorse using, buying or preparing any unapproved product. Talk to a licensed clinician before you start, stop or change any treatment.