MK-677
The only orally active GH secretagogue. Studied in multiple Merck clinical trials.
Mechanism of Action
Bioregulator compound with targeted biochemical activity.
Evidence Chain
MK-677
COMPOUND
1 Research Goal
• Muscle & Tissue Growth
Evidence Strength
2 articles sourced
Knowledge Graph
(3 connections)Research Evidence
(2)Growth Hormone Secretagogues and IGF-1 Axis Research
Examination of GHRH, GHRP, and ghrelin mimetic mechanisms in GH secretion and IGF-1 axis research.
Peptide Synergy: Growth Hormone Secretagogue Stacking
Evidence-based review of GH secretagogue peptide synergy, examining pulsatile GH release, receptor mechanisms, and combination protocols.
Overview
MK-677 (Ibutamoren) is a non-peptide, orally active growth hormone secretagogue developed by Merck. Unlike peptide-based GHS compounds, MK-677 is a small molecule that mimics the action of ghrelin at the GHS-R1a receptor. It is the only orally active GH secretagogue that has progressed to advanced clinical trials, making it unique in the GHS research landscape. MK-677 has been studied in multiple Merck clinical trials for frailty, osteoporosis, and growth hormone deficiency.
Mechanism of Action
MK-677 acts as a potent, orally bioavailable agonist of the ghrelin receptor (GHS-R1a), stimulating the release of endogenous growth hormone from the pituitary gland. Unlike exogenous GH, MK-677 preserves the natural pulsatile pattern of GH secretion and maintains feedback regulation via somatostatin. The oral bioavailability of MK-677 (approximately 60%) eliminates the need for injection, a significant advantage over peptide-based GHS compounds. MK-677 produces sustained elevations in IGF-1 levels with once-daily oral dosing, with effects lasting 24+ hours.
Research Highlights
Clinical studies have demonstrated MK-677's efficacy in increasing GH and IGF-1 levels in elderly subjects, with sustained elevation over 12-month treatment periods. Research showed improvements in muscle mass, bone density markers, and sleep quality in elderly populations. Studies explored its potential in osteoporosis, frailty, and recovery from hip fracture. Research also investigated its effects on appetite stimulation and body composition. Despite promising results, MK-677 was not advanced to FDA approval, reportedly due to concerns about sustained IGF-1 elevation and regulatory considerations.
Dosage & Administration
In clinical trials, MK-677 was administered orally at doses of 10-50 mg once daily, typically in the morning. The 25 mg dose was most commonly studied. For research use only (RUO).
Safety Profile
Clinical trials reported generally favorable safety profiles, with common side effects including increased appetite, transient water retention, muscle pain, and mild hyperglycemia. Concerns about sustained IGF-1 elevation and potential long-term effects contributed to the discontinuation of development. Fasting blood glucose increases were observed in some studies. Not approved by the FDA for any indication.
References
Chapman IM, et al. MK-677 in elderly subjects. J Clin Endocrinol Metab. 1996. Bach MA, et al. MK-677 and bone density. J Clin Endocrinol Metab. 2004. Nass R, et al. MK-677 and sleep. Clin Endocrinol. 2015. All content is for educational and research purposes only.
Related Compounds
Synergy & Compatibility
(5)Computational assessment of bio-regulatory compatibility with compounds sharing research goals. Scores reflect half-life alignment, receptor target overlap, and bioavailability data.
Computational assessment based on available pharmacology data. Does not account for individual variability, dose-dependent effects, or unstudied interactions. For research use only.
Community Observations
(0)Qualitative, self-reported researcher observations. Distinct from peer-reviewed evidence — not medical advice.
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For research use only. Not medical advice.