Also known as: Ibutamoren · Ibutamoren Mesylate · L-163,191 · MK-0677 · Nutrobal
MK-677 (Ibutamoren) is a potent, orally active non-peptide growth hormone secretagogue receptor (GHSR-1a) agonist that mimics ghrelin. Unlike injectable GH peptides, it provides sustained GH and IGF-1 elevation through once-daily oral dosing. Clinical trials demonstrate 40–90% IGF-1 increases, lean mass gains, improved sleep architecture, and bone density benefits at 25 mg/day. Currently the only orally bioavailable GH secretagogue with extensive human trial data.
MK-677 (Ibutamoren) is a non-peptide small molecule developed by Merck in the 1990s using their spiroindanyl-piperidine scaffold. It is one of the most extensively studied growth hormone secretagogues (GHS) with published Phase 2 and Phase 3 human trial data spanning healthy adults, elderly populations, GH-deficient patients, and Alzheimer's disease trials.
Unlike injectable GH peptides (sermorelin, ipamorelin, CJC-1295), MK-677 is orally bioavailable, has a plasma half-life of approximately 24 hours, and can maintain elevated GH and IGF-1 levels with once-daily dosing. It does not suppress the pituitary's own GH axis — instead, it amplifies pulsatile GH secretion by mimicking ghrelin at GHSR-1a receptors in the pituitary and hypothalamus.
Its oral route, long half-life, and established safety profile make it the most practical GH secretagogue for extended research use. Phase 2 data in healthy young men showed mean IGF-1 increases of 72% at 25 mg/day after 2 weeks. In elderly adults, 2-year treatment normalized IGF-1 levels and produced significant lean mass gains (1–2 kg) without proportional fat gain — a meaningful benefit in the context of age-related sarcopenia.
MK-677 binds GHSR-1a (growth hormone secretagogue receptor 1a) on pituitary somatotroph cells and hypothalamic neurons with high affinity (Ki ~1 nM). GHSR-1a activation triggers phospholipase C → IP3/DAG → intracellular calcium release → GH exocytosis. As a full agonist, MK-677 robustly amplifies GH pulse amplitude beyond physiological ghrelin levels.
GHSR-1a stimulation during slow-wave sleep (SWS) preferentially amplifies the nocturnal GH pulse — the largest natural GH peak in humans. Bedtime MK-677 dosing aligns with this circadian window, significantly increasing mean nocturnal GH amplitude. Clinical sleep EEG studies confirm increased REM and SWS duration in MK-677-treated subjects — a mechanism underlying reports of enhanced sleep quality and vivid dreaming.
Sustained GH elevation drives hepatic IGF-1 secretion via JAK2/STAT5b signaling in hepatocytes. Circulating IGF-1 binds IGF-1R on muscle, bone, and other tissues to activate PI3K/Akt/mTOR (protein synthesis, anti-catabolism) and ERK1/2 (cell proliferation). This underpins the lean mass accretion and bone density improvements in clinical trials, and explains the increase in appetite (ghrelin-mediated, via NPY/AgRP neurons).
MK-677 is the only orally bioavailable GH secretagogue with extensive human trial data. Its 24-hour half-life makes once-daily dosing practical. Expect increased appetite (nearly universal), mild water retention in the first 2–4 weeks, and vivid dreams. Monitor fasting glucose periodically — mild insulin resistance is dose-dependent. Not suppressive of the pituitary GH axis.
Unlike injectable GH peptides, MK-677 does not require pulsatile dosing or short cycle periods. 2-year continuous use was studied in elderly adults with acceptable safety. For research contexts, 12–16 week cycles are common, with a washout period before resuming. IGF-1 levels should be monitored every 8–12 weeks during use.
Not approved for human therapeutic use outside clinical trials. Monitor blood glucose — mild fasting hyperglycaemia is possible, especially in insulin-resistant individuals. Not recommended for active cancer or known insulin resistance without monitoring.
Phase 2 healthy young adults (Svensson et al., J Clin Endocrinol Metab, 1998): MK-677 25 mg/day × 14 days produced 72% mean IGF-1 increase vs. 2% placebo. GH 24-hour secretion rate increased 97%. No adverse effects on fasting glucose, insulin, or cortisol at this dose and duration.
Phase 2 elderly adults (Nass et al., J Clin Endocrinol Metab, 2008): 2-year randomized trial in 65+ adults. MK-677 25 mg normalized IGF-1 to young-adult levels throughout. Lean body mass increased significantly (+1.6 kg vs. baseline). Fat mass was not significantly different. Mild increase in fasting glucose and insulin resistance observed — manageable but requiring monitoring in insulin-resistant individuals.
Phase 2 hip fracture recovery: MK-677 25 mg accelerated functional recovery and reduced hospital length of stay vs. placebo, attributed to IGF-1-mediated improvement in muscle mass and bone repair.
Adverse effects: Increased appetite (nearly universal at 25 mg), mild transient edema, fatigue, mild fasting glucose elevation. Insulin resistance is dose-dependent — particularly relevant in pre-diabetic individuals. Does not suppress endogenous GH axis or cause HGH-associated side effects (acromegaly, organ growth) at standard doses.
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