MK-677 (Ibutamoren): Research, Mechanism & Current Evidence

What is MK-677?

MK-677, also called ibutamoren, is a small molecule rather than a peptide, which is why it works as a tablet where injectable peptides in the same family do not. It was developed by Merck.

It reached substantial clinical trials but was never approved, and development was discontinued.

Status: Not an approved medicine. Prohibited in sport by WADA.

What is MK-677 researched for?

Growth hormone and IGF-1 levels in healthy older adults and in growth hormone deficiency.

Muscle mass and bone density in older populations, and body composition during periods of restricted movement.

Appetite stimulation, studied in the context of cachexia.

• Restores youthful growth hormone levels in elderly subjects with 97% increase in 24-hour secretion.
• Sustained 40-72% IGF-1 elevation over extended periods.
• 20% REM increase in younger adults; 50% improvement in elderly.
• Demonstrates +2.69g/day nitrogen retention versus -8.97g/day placebo, protecting lean mass during caloric restriction.
• Increases fat-free mass with preferential lean tissue accrual.
• 15% basal metabolic rate elevation documented at 2 weeks.
• 39-45% increase in bone formation markers within 6-8 weeks.

How does MK-677 work?

MK-677 activates the ghrelin receptor, the same target as injectable growth hormone-releasing peptides, prompting the pituitary to release its own growth hormone.

Because it is orally bioavailable and long-acting, it produces a sustained elevation rather than the sharp pulses seen with short-acting injectables — a difference that matters to how growth hormone physiology is normally regulated.

Reported targets: GHS-R1a, ghrelin receptor

What does the research show?

Trials in older adults reliably showed increases in growth hormone and IGF-1 and modest gains in lean mass. A widely cited two-year study reported increased lean mass without a corresponding improvement in strength or function.

Reported effects include increased appetite, water retention and reductions in insulin sensitivity.

Limitations of the current evidence

Increased lean mass without improved function is a recurring result and an important caveat.

Reduced insulin sensitivity and raised fasting glucose were observed in trials, which is directly relevant to any metabolic research context.

Development was discontinued, so long-term safety data does not exist.

References

1. Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men

   Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, et al. · The Journal of clinical endocrinology and metabolism · 1996

   Randomized, double-blind crossover in 9 healthy young men. 7-day oral MK-677 (5 and 25mg) increased 24-hour GH profiles dose-dependently while preserving circadian patterns.

   Controlled clinical trial · PMID 8768828

2. Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects

   Chapman, I.M., et al. · Journal of Clinical Endocrinology & Metabolism · 1996

   Randomized, double-blind trial in 32 elderly subjects (64-81 years). 25mg/day MK-677 for up to 4 weeks increased mean 24-hour GH by 97% and restored IGF-I concentrations to young adult levels.

   Controlled clinical trial

3. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man

   Copinschi G, Leproult R, Van Onderbergen A, et al. · Neuroendocrinology · 1997

   In young adults, 25mg MK-677 increased stage IV sleep duration by 50% and REM sleep by 20%. In older adults, REM sleep increased nearly 50% with decreased REM latency. Sleep deviations dropped from 42% to 8%.

   PMID 9349662

4. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism

   Murphy MG, Plunkett LM, Gertz BJ, et al. · The Journal of clinical endocrinology and metabolism · 1998

   Double-blind crossover in 8 healthy volunteers under caloric restriction. 25mg/day MK-677 for 7 days reversed nitrogen wasting (+2.69g/day vs -8.97g/day placebo) and significantly increased IGF-I.

   Controlled clinical trial · PMID 9467534

5. Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure

   Svensson J, Lönn L, Jansson JO, et al. · The Journal of clinical endocrinology and metabolism · 1998

   24 obese males treated with 25mg/day for 8 weeks showed sustained increases in GH, IGF-I, fat-free mass, and a transient increase in basal metabolic rate at 2 weeks.

   PMID 9467542

6. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults

   Murphy, M.G., et al. · Journal of Bone and Mineral Research · 1999

   187 elderly adults (65+) across three placebo-controlled studies. 9 weeks of MK-677 increased serum osteocalcin by 29.4%, bone-specific alkaline phosphatase by 10.4%, and urinary NTX by 22.6%.

   Controlled clinical trial

7. 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, et al. · Annals of internal medicine · 2008

   12-month RCT in 65 healthy adults (60-81 years). MK-677 increased GH and IGF-I to young adult levels, increased fat-free mass while placebo group declined, and was generally well tolerated.

   Controlled clinical trial · PMID 18981485

8. Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group

   Murphy MG, Bach MA, Plotkin D, et al. · Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 1999

   PMID 10404019

9. 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, et al. · The Journal of clinical endocrinology and metabolism · 1996

   PMID 8954023

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