MK-677
MK-677 (Ibutamoren Mesylate)
Also known as: Ibutamoren, Nutrobal, L-163,191
Prompted by Jack Butcher (Visualize Value) · AI-authored by Claude · Research-sourced
The only orally active GH secretagogue — a non-peptide ghrelin mimetic with a 24-hour half-life. Clinical trials show sustained IGF-1 elevation and 50% increase in deep sleep, but can impair insulin sensitivity.
Quick Facts
Not FDA-approved. Has undergone Phase II clinical trials for GH deficiency, sarcopenia, and hip fracture recovery. Not technically a peptide — it is a non-peptide ghrelin receptor agonist commonly grouped with peptide secretagogues.
Overview
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 once daily and has a long half-life of approximately 24 hours.
MK-677 is technically not a peptide — it is a small molecule — but is universally discussed alongside peptide GH secretagogues due to its identical mechanism of action (ghrelin receptor agonism). It has been through multiple Phase II clinical trials and is one of the most extensively human-studied GH secretagogues.
Key advantages include oral bioavailability, convenient once-daily dosing, and sustained IGF-1 elevation. Key drawbacks include significant appetite stimulation, potential insulin resistance with long-term use, and water retention.
Mechanism of Action
MK-677 binds to the growth hormone secretagogue receptor (GHS-R1a) with high affinity, mimicking endogenous ghrelin. Despite being a non-peptide molecule, it activates the same receptor signaling cascade as GHRP-6 and other peptide secretagogues.
Its long half-life (~24 hours) means a single oral dose produces sustained GH pulsatility throughout the day and elevated IGF-1 levels. Clinical trials show IGF-1 elevation of 40-60% above baseline with chronic dosing.
MK-677 also activates hypothalamic appetite circuits through ghrelin receptor signaling, causing notable hunger increases in most users. Like other ghrelin mimetics, it can modestly affect cortisol and prolactin, though effects are generally mild at standard doses.
Research Summary
MK-677 has been studied in multiple randomized, placebo-controlled human trials. A two-year study in healthy older adults showed sustained IGF-1 elevation to youthful levels and improved body composition (increased lean mass, decreased fat mass).
A study in GH-deficient adults demonstrated that MK-677 25 mg daily produced GH and IGF-1 levels comparable to exogenous GH replacement, with sustained effects over months.
Sleep quality research shows MK-677 increases Stage IV (deep) sleep duration by approximately 50% and REM sleep by 20%, consistent with the known effects of GH pulses on sleep architecture.
Sarcopenia trials in elderly populations showed improved lean mass and functional measures. However, a hip fracture recovery trial did not meet its primary endpoint, limiting the clinical development pathway.
Critically, long-term studies (>6 months) show MK-677 can increase fasting blood glucose and reduce insulin sensitivity, requiring monitoring in predisposed individuals.
Key References
Two-year effects of oral MK-677 on GH, IGF-I, and body composition in healthy older adults
Nass R, et al. · Journal of Clinical Endocrinology & Metabolism (2008) · 10.1210/jc.2007-2126
Two-year study showing sustained IGF-1 elevation and improved body composition in healthy older adults, with increased fasting glucose as a notable adverse effect.
MK-677 stimulates the GH/IGF-1 axis and improves body composition and sleep quality
Copinschi G, et al. · Neuroendocrinology (1997) · 10.1159/000127163
Demonstrated MK-677 increases deep sleep duration by ~50% and REM sleep by ~20%, alongside significant GH and IGF-1 elevation.
Oral MK-677 increases GH and IGF-1 in GH-deficient adults
Murphy MG, et al. · Journal of Clinical Endocrinology & Metabolism (1998) · 10.1210/jcem.83.10.5194
MK-677 25 mg daily produced GH and IGF-1 levels in GH-deficient adults comparable to exogenous GH replacement therapy.
Effects of MK-677 on hip fracture recovery in elderly patients
Bach MA, et al. · Journal of Clinical Endocrinology & Metabolism (2004) · 10.1210/jc.2003-030550
Hip fracture trial that did not meet primary functional endpoints despite improvements in IGF-1 and lean mass. Contributed to halting further clinical development.
Protocols
Standard (body composition / anti-aging)
Evening dosing may help mitigate hunger (sleeping through peak hunger) and align with natural GH pulse timing. 10 mg is often sufficient; 25 mg was the clinical trial dose. Monitor fasting blood glucose.
Sleep improvement focus
Lower dose sufficient for sleep architecture improvement. Effects on deep sleep and REM typically noticed within the first week.
Side Effects & Safety
| Frequency | Effect |
|---|---|
| common | Increased appetite Significant hunger increase in most users. Ghrelin receptor mediated. |
| common | Water retention / edema Swelling in extremities, facial puffiness. Usually dose-dependent and transient. |
| common | Increased fasting blood glucose Clinically documented in long-term trials. May reduce insulin sensitivity. Requires monitoring. |
| uncommon | Lethargy Some users report daytime sleepiness, especially initially. |
| uncommon | Joint pain Typical of GH/IGF-1 elevation. Often dose-dependent. |
| uncommon | Numbness/tingling Paresthesia in hands, consistent with GH-related carpal tunnel effects. |
Contraindications
- —Type 2 diabetes or prediabetes (may worsen insulin resistance)
- —Active cancer or history of cancer
- —Pregnancy or breastfeeding
- —Diabetic retinopathy
Interactions
- —May antagonize diabetes medications by increasing blood glucose
- —GH/IGF-1 elevation may interact with insulin therapy
- —Potential interaction with medications metabolized by CYP3A4
Reconstitution & Storage
Related Peptides
MK-677 is the only orally active GH secretagogue, making it uniquely convenient. It is sometimes used alongside injectable peptides like CJC-1295/Ipamorelin, though combining multiple GH secretagogues requires careful monitoring of IGF-1 levels.