MK-677 (Ibutamoren): What the Research Shows About This Oral GH Secretagogue

What it is

MK-677, also called ibutamoren, is not a peptide. It is a small molecule that Merck designed in the 1990s to do what ghrelin-type peptides like GHRP-6 do, trigger growth hormone release through the ghrelin receptor, but as a pill that lasts about 24 hours. It is on this site because it is sold and discussed alongside peptides, and because it has more human trial data than most of them.

Merck tested it for growth hormone deficiency, frailty in the elderly, and hip-fracture recovery. It never reached Phase III and was never approved. It is now a research chemical, usually sold by the same vendors as SARMs, which is how it acquired the false reputation of being one.

What it is studied for

Restoring growth hormone and IGF-1 in older adults, the main trial. Body composition, bone density, deep sleep, and recovery after hip fracture, all in smaller studies.

What the evidence actually shows

In humans

The key study followed 65 healthy adults aged 60 to 81 for two years, half on 25 mg of MK-677 a day, half on placebo. MK-677 raised growth hormone and IGF-1 to the levels of healthy young adults and kept them there for the full two years without the pituitary tiring (Nass et al., 2008). That is the clearest demonstration in this whole class that a ghrelin mimic can hold IGF-1 up long term.

The body changes were smaller than the hormone changes. Lean mass rose by about 1.1 kg over a year, fat mass rose slightly rather than falling, and strength and function did not improve measurably. An earlier two-week study in obese men had shown a 40% rise in IGF-1 with growth hormone pulses that looked younger (Chapman et al., 1996). In older adults recovering from hip fracture, MK-677 improved some functional measures without a clear gain in muscle (Murphy et al., 2001).

Sleep is the most consistent subjective result. In young men, a week of MK-677 increased deep (stage IV) sleep by about half and REM sleep by a fifth (Copinschi et al., 1997). Bone density markers rose in the two-year study, though the study could not measure fracture risk.

From user reports

Hunger within days, often intense. Better sleep within a week. Puffy hands and face from water retention. Over months, gradual improvements in recovery and a fuller look that users attribute to muscle and that may be partly water. Some report numb or tingling hands.

How it works

MK-677 binds the ghrelin receptor and makes the pituitary release growth hormone in pulses, which raise IGF-1. Because it stays active for a day, the pulses keep coming, and IGF-1 sits elevated continuously. The feedback loops stay intact, so the pituitary keeps responding, which the two-year trial confirmed. The same receptor drives hunger, which is why appetite rises so reliably.

How it is used in studies

The trials used 25 mg once a day by mouth. Users take 10 to 25 mg at bedtime, to line the growth hormone pulses up with sleep and to sleep through the hunger, in runs of 8 to 16 weeks or continuously. It needs no injection, mixing, or refrigeration.

Side effects and unknowns

From the trials: increased appetite, water retention and swelling, higher fasting glucose with reduced insulin sensitivity, tiredness in the first weeks, and tingling in the hands. The blood-sugar effect is the one to take seriously. In the two-year study, fasting glucose rose and insulin sensitivity fell; for anyone already near prediabetes, that is movement in the wrong direction without symptoms to warn you.

The long-term unknown is cancer. IGF-1 promotes cell growth, and chronically high IGF-1 is linked in population studies to some cancers. No MK-677 trial found a signal, and no trial was long or large enough to. Two years of a raised IGF-1 in 32 people does not answer the question for ten years in thousands. See the safety guide.

How it compares

• Ipamorelin: the injectable equivalent, a short pulse instead of an all-day rise, with far less hunger and almost no human data.
• GHRP-2 and GHRP-6: injected, stronger pulses, more cortisol.
• CJC-1295 and sermorelin: GHRH-type, a different receptor; people stack MK-677 with them, untested.
• SARMs: not related. MK-677 does not touch the androgen receptor. See peptides vs SARMs vs steroids.

Legal status

Not approved in any country. Sold as a research chemical. Not a controlled substance in the United States. WADA bans it in and out of competition.

Bottom line

MK-677 is the best-studied compound in its class and the results are honest: it raises growth hormone and IGF-1 as promised, holds them there for years, and turns that into only a small amount of muscle, no fat loss, better sleep, more hunger, and worse blood sugar. It proves the hormone story and undercuts the body-transformation story in the same trial.

References

1. Nass R, et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. PubMed
2. Chapman IM, et al. (1996). 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. J Clin Endocrinol Metab. PubMed
3. Murphy MG, et al. (2001). Effect of ibutamoren mesylate (MK-677) on the recovery of hip fracture patients. Clin Endocrinol. PubMed
4. Copinschi G, et al. (1997). Effects of a 7-day treatment with a novel, orally active, growth hormone secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men. J Clin Endocrinol Metab. PubMed

See also

• Peptide
  GHRP-2: What the Research Shows About This Second-Generation GH Secretagogue

  GHRP-2 is a six-amino-acid peptide that copies ghrelin, the hunger hormone, to make the pituitary release a pulse of growth hormone. Japan approved it as a one-dose diagnostic test; no one has trialed it as a treatment.

• Peptide
  GHRP-6: What the Research Shows About This Growth Hormone Releasing Peptide

  GHRP-6 is the six-amino-acid peptide that led to the discovery of the ghrelin receptor. It reliably releases growth hormone in people and makes them very hungry. No trial has tested it for muscle or recovery.

• Peptide
  CJC-1295: What the Evidence Says About This GHRH Analog

  CJC-1295 is a longer-lasting version of GHRH, the signal that tells the pituitary to release growth hormone. The DAC form raised GH and IGF-1 for days in one small trial; the no-DAC form (Mod GRF 1-29) has no human trial of its own.