MK-677

In simple words

MK-677 (ibutamoren) is not a peptide but a small molecule taken as a pill that mimics the "hunger hormone" and increases growth hormone production. It has been studied for years: it increased muscle mass and improved deep sleep, but it can raise blood sugar.

What this molecule is

NOT a peptide. A small-molecule spiro compound, C₂₇H₃₆N₄O₅S. Oral GHS-R1a agonist. ~528 Da. T½ ~24 h of effect on GH.

Why it is studied

The only oral GH secretagogue with large RCTs. Ann Intern Med (2 years, n=65): ↑fat-free mass +1.6 kg, ↑GH to youthful levels. ↑stage IV deep sleep +50%, ↑REM +20%. Convenient: tablet/capsule.

How it works

Mimics ghrelin at GHS-R1a → ↑pulsatile GH secretion. Unlike peptides, it is resistant to proteases (not a peptide). Additionally: ↑appetite via NPY/AgRP. Does not suppress the body's own GH secretion.

Doses used in studies

Studies used 25 mg/day orally at night (synchronized with the nighttime peak) without titration; course length in studies was up to 2 years.

Combined with in studies

• Sermorelin / Mod-GRF — GHS-R1a + GHRHR: different receptors → synergy
• Exogenous GH — DO NOT combine

Level of evidence

Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. 4 human RCTs, including a 2-year trial.

Important to know

⚠️ NOT a peptide (included because of its GHS-R1a mechanism). Not FDA-approved. Banned by WADA (S2). ↑appetite in most subjects, edema, arthralgia, ↑fasting glucose (↑insulin resistance with long-term use). The Phase IIb trial (hip fractures) was stopped because of heart failure in older adults. Long-term (>6 months) → risk of insulin resistance.

Studies in PubMed

1. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. (Ann Intern Med, 2008)
2. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. (Neuroendocrinology, 1997)
3. Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study. (Nephrol Dial Transplant, 2018)
4. 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)
5. MK0677, a Ghrelin Mimetic, Improves Neurogenesis but Fails to Prevent Hippocampal Lesions in a Mouse Model of Alzheimer's Disease Pathology. (J Alzheimers Dis, 2019)