Growth Hormone Secretagogue
MK-677
Also known as: Ibutamoren
An orally active, non-peptide growth hormone secretagogue (a 'ghrelin mimetic') with a substantial human clinical trial history in older adults, including a 12-month randomized trial — and a clear, verified failure to slow Alzheimer's disease progression in a dedicated trial.
Overview
MK-677 (ibutamoren) is worth flagging as structurally different from most compounds on this site: it's a small-molecule, non-peptide growth hormone secretagogue, orally active (not requiring injection), which acts on the same ghrelin receptor (GHS-R1a) pathway as injectable secretagogues like ipamorelin or hexarelin.
Proposed Mechanism of Action
MK-677 agonizes GHS-R1a, stimulating pulsatile growth hormone release and downstream IGF-1 production — mechanistically similar to peptide-based secretagogues, but achieved with an orally bioavailable small molecule rather than an injectable peptide.
Research Context
MK-677 has a genuinely substantial human trial history relative to most compounds here. The Chapman et al. (1996) trial showed 25 mg/day oral MK-677 normalized IGF-1 levels in healthy elderly subjects within 4 weeks. The Nass et al. (2008) trial extended this to 12 months in older adults, finding sustained increases in fat-free mass alongside increased GH/IGF-1 — but also documented real tradeoffs: declining insulin sensitivity and increased fasting glucose, and no measurable improvement in strength or function despite the body-composition changes. Separately, a dedicated trial testing MK-677 for slowing Alzheimer's disease progression found clear target engagement (IGF-1 rose as expected) but no clinical benefit — the drug did not slow disease progression despite doing what it was mechanistically supposed to do.
Limitations of the Current Evidence
- Increased fat-free mass in the 12-month trial did not translate to improved strength or physical function — a meaningful gap between a biomarker/body-composition change and a functional outcome.
- Fasting glucose and insulin sensitivity worsened during treatment in the same trial — a real metabolic tradeoff, not a hypothetical one, that's directly documented in human data.
- The Alzheimer's trial is a clear, direct example of a compound successfully engaging its target (elevated IGF-1) while still failing to produce the clinical outcome it was tested for — useful context for how much weight to put on biomarker changes generally, for this compound or others.
Research-Setting Dosing (as reported in literature)
| Route | Range (as reported) | Frequency | Notes |
|---|---|---|---|
| Oral | 25–25 mg | Once daily | The 25 mg/day dose restored serum IGF-I concentrations to the normal range for young adults within 4 weeks in Chapman et al. (1996); the same dose was used in the 12-month Nass et al. (2008) trial. |
Figures above are extracted directly from the cited preclinical/research literature. They describe what researchers administered to study subjects (frequently animal models) — they are not human dosing recommendations and are not medical advice.
Cited Studies
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial
Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO · Annals of Internal Medicine · 2008
Human clinical trial (randomized, 12 months, healthy older adults)View source →Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects
Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO · Journal of Clinical Endocrinology & Metabolism · 1996
Human clinical trial (4 weeks, healthy elderly subjects)View source →
Last updated August 1, 2026