Growth HormoneResearch strength: ModerateEvidence: Moderate

MK-677

Ibutamoren (oral ghrelin receptor agonist)

Also known as: Ibutamoren, MK-0677

A non-peptide, orally active ghrelin receptor agonist that raises growth hormone and IGF-1. Completed but did not pass Phase 3 for approval.

Overview

MK-677 stimulates pituitary growth hormone secretion by mimicking ghrelin. Unlike injectable secretagogues it is orally active with a long half-life. It was studied through a two-year trial in older adults and a Phase 2b hip-fracture recovery trial (stopped early for a heart-failure safety signal) but was never approved. It is studied for lean mass, bone density, and sleep architecture.

Mechanism of action

Agonizes the ghrelin/GH secretagogue receptor (GHS-R1a), increasing GH and IGF-1 while also stimulating appetite.

Key studies & citations

Human2008
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial
65 adults aged 60 to 81 on MK-677 25 mg daily for up to 2 years: GH and IGF-1 rose to young-adult levels and fat-free mass increased 1.1 kg vs a 0.5 kg loss on placebo, but strength and function did not improve and fasting glucose and insulin resistance rose.
Annals of Internal Medicine
Human2011
MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study
123 elderly hip-fracture patients: gait speed improved and IGF-1 rose, but most functional measures did not, and the trial was terminated early over a congestive heart failure safety signal.
Archives of Gerontology and Geriatrics
Human1997
Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man
Crossover study in young and older adults: high-dose MK-677 increased stage IV sleep by about 50% and REM sleep by more than 20% in young subjects.
Neuroendocrinology