MK-677

Overview

MK-677 (ibutamoren, MK-0677, L-163,191) is an orally active, non-peptide small-molecule growth hormone secretagogue developed by Merck in the 1990s. It is a spiropiperidine ghrelin-receptor (GHSR-1a) agonist — not a peptide and not a SARM, though it is commonly misclassified as both in grey-market retail. Merck discontinued development after mixed efficacy and adverse metabolic / cardiovascular findings; it is not FDA-approved.

Mechanism of Action

MK-677 is a selective agonist of the ghrelin receptor (GHSR-1a) on pituitary somatotrophs and hypothalamic neurons, driving pulsatile GH release and secondary IGF-1 elevation with once-daily oral dosing. Oral bioavailability is sufficient for sustained 24-hour effect. Unlike GHRPs, it does not significantly raise cortisol or prolactin at typical doses. It also stimulates appetite through hypothalamic ghrelin signaling.

Research Summary

Short-term trials showed ~25–40% IGF-1 elevation and reversal of diet-induced nitrogen wasting (Murphy 1998, JCEM). A 2-year randomized trial in healthy older adults (Nass 2008, Ann Intern Med) restored GH/IGF-1 to young-adult levels and increased fat-free mass, but produced modest fasting glucose elevation and insulin resistance. A Phase IIb hip-fracture trial (Adunsky 2011) was halted early after a congestive heart failure safety signal (4/62 ibutamoren vs 1/60 placebo). Merck abandoned the program; the compound remains investigational with no approved indication.

Dosing Information

Reported Side Effects

• Marked appetite increase (ghrelin-mediated)
• Water retention, edema, and fluid-driven weight gain
• Elevated fasting glucose and reduced insulin sensitivity
• Lethargy and drowsiness
• Paresthesias (numbness/tingling in extremities)
• Muscle aches and joint stiffness (fluid-related)
• Worsening of pre-existing congestive heart failure (documented trial signal)

Research References

• Murphy et al. — MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism (JCEM 1998) (1998)
• Nass et al. — Effects of an oral ghrelin mimetic (MK-677) on body composition and clinical outcomes in healthy older adults (Ann Intern Med 2008) (2008)
• Svensson et al. — Two-month treatment of obese subjects with the oral GH secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure (JCEM 1998) (1998)
• Copinschi et al. — Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man (Neuroendocrinology 1997) (1997)
• Adunsky et al. — MK-0677 (ibutamoren mesylate) for patients recovering from hip fracture: Phase IIb trial halted early for CHF safety signal (Arch Gerontol Geriatr 2011) (2011)