MK-677
Non-peptide oral ghrelin mimetic that elevates GH and IGF-1 levels for up to 24 hours.
🔬 Mechanism of Action
MK-677 (Ibutamoren) is a non-peptide, orally-active growth hormone secretagogue that mimics ghrelin at the GHS-R1a receptor. Unlike injectable GH secretagogues, MK-677 is taken orally and has a long duration of action — a single daily dose elevates GH and IGF-1 levels for up to 24 hours. It does not suppress natural GH secretion, and studies show sustained efficacy over 12+ months without desensitization.
MK-677 increases lean body mass, improves sleep quality (particularly REM sleep depth), and enhances bone mineral density. It is commonly included in peptide discussions despite being a non-peptide small molecule because it targets the same receptor as peptide GHRPs.
Source: PMID: 9467534
📜Background & History
MK-677 (Ibutamoren) is an orally active non-peptide ghrelin mimetic developed by Merck in the 1990s. Unlike injectable GHRPs, its oral bioavailability (~60%) and 24-hour half-life enable once-daily dosing. Phase I/II trials (Murphy et al., NEJM 1998) demonstrated sustained GH and IGF-1 elevation over 12 months with improvement in lean body mass in elderly subjects. Despite multiple clinical trials, it has never been approved as a pharmaceutical. It remains the most widely used oral GH secretagogue in research and wellness contexts.
🎯 Research Use Cases
- ✓Oral GH elevation without injections — ideal for injection-averse users
- ✓Age-related GH deficiency (somatopause) management
- ✓Muscle mass preservation in caloric restriction or aging
- ✓Improved deep sleep quality via GH-mediated slow-wave sleep enhancement
- ✓IGF-1 elevation for recovery and cellular repair
💉 Dosing Protocol
| Typical Dose | 10-25 mg/day (oral) |
| Frequency | 1× daily (oral) |
| Half-Life | ~5 hours (IGF-1 elevation 24h) |
⚠️Safety & Considerations
MK-677 is not FDA-approved. It increases appetite and may elevate blood glucose levels and water retention. Monitor fasting glucose regularly. Not suitable for diabetics without medical supervision. Does not require reconstitution — oral dosing.
⚡Interactions & Contraindications
Elevates fasting glucose and insulin — do not use with insulin resistance, pre-diabetes, or T2D without medical supervision. Water retention common at higher doses. Hunger stimulation (ghrelin effect) makes caloric restriction difficult. May exacerbate sleep apnea. Avoid combining with GLP-1 agonists (opposing metabolic effects).
🔗Synergies & Common Stacks
Dual-pathway GH elevation: CJC-1295 via GHRH receptor and MK-677 via ghrelin receptor. Additive effect on GH/IGF-1 with convenient weekly + daily dosing.
MK-677 elevates GH/IGF-1 for systemic anabolic effects; BPC-157 handles tissue-specific repair — useful combined recovery protocol.
❓ Frequently Asked Questions
Is MK-677 a peptide?▼
What is the standard MK-677 dose?▼
Does MK-677 cause desensitization?▼
📖 References
- Murphy MG, et al. “MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.” J Clin Endocrinol Metab (1998). PMID: 9506738
- Nass R, et al. “Two-year effects of MK-677 on body composition in elderly adults.” J Clin Endocrinol Metab (2008). PMID: 18544658