MK-677 (Ibutamoren): Oral Ghrelin Mimetic / GH Secretagogue
Oral, once-daily non-peptide ghrelin receptor agonist. Raises GH and IGF-1 but failed Phase 3 for sarcopenia; not an approved medicine.
👥 Human studies
- Full name
- Ibutamoren mesylate (MK-0677)
- Class
- Ghrelin receptor (GHS-R1a) agonist — non-peptide
- Half-life
- ~4–6 hours (IGF-1 response sustained)
- Route
- Oral daily
- Developer
- Merck → Reverse Pharmacology
- Regulatory status
- No approval; investigational; WADA-banned
What it is
MK-677 is an oral non-peptide small molecule that mimics ghrelin at the GHS-R1a receptor, producing a pulsatile-like increase in growth hormone secretion from the pituitary. Because it is orally bioavailable, it generated strong interest for sarcopenia, GH deficiency, and anti-aging indications.
How it works
Agonism at GHS-R1a on pituitary somatotrophs increases GH release. GH in turn stimulates hepatic IGF-1 production. Unlike peptide GH secretagogues, MK-677 is orally active with a long duration of effect.
The physiological GH/IGF-1 elevation is meaningful (25–100% above baseline) and sustained for weeks. However, food-intake increases via ghrelin action, and water retention via the GH-IGF-1 axis, are common.
What the research shows
Phase 2 studies in healthy older adults showed biomarker responses; the pivotal Phase 3 sarcopenia trial failed its functional endpoint.
Nass R. et al. (2008) — older adults body composition
Nass R. et al., Ann Intern Med 2008;149:601–611. 👥 Human studies
65 healthy adults aged 60–81 received MK-677 25 mg/day or placebo for 12 months.
Fat-free mass increased ~1.1 kg; IGF-1 rose into the range of healthy young adults. No improvement in strength or physical performance was seen.
Limitations: Small; no functional benefit despite biomarker changes; transient glucose intolerance.
Adunsky A. et al. (2011) — hip-fracture rehabilitation (Phase 3)
Adunsky A. et al., J Am Geriatr Soc 2011;59:1410–1418. 👥 Human studies
~400 patients recovering from hip fracture randomised to MK-677 or placebo for up to 24 weeks.
The trial failed its primary functional endpoint. Pharmaceutical development was halted.
Limitations: Phase 3 negative; led to programme discontinuation.
Safety and limitations
Common: increased appetite, mild oedema, arthralgias, transient worsening of insulin sensitivity and glucose tolerance. Rare: congestive heart failure signals in frailer older adults in Phase 3.
MK-677 is widely sold in unregulated markets as a research chemical. Long-term effects on insulin resistance and cardiac remodelling are unknown.