MK-677

An orally active compound that mimics ghrelin, stimulating growth-hormone and IGF-1 release. Chemically not a peptide, but pharmacologically adjacent to the GH-secretagogue peptides in the catalog. Never approved; studied for frailty and GH deficiency.

MK-677 (ibutamoren) is an orally active ghrelin-receptor agonist — it mimics ghrelin, the hunger hormone, at the receptor that triggers growth-hormone release. So it raises GH and, downstream, IGF-1, without being growth hormone itself and without an injection. The ghrelin action is also why the appetite increase is not a side effect but a direct consequence of the mechanism, and why water retention and blood-sugar effects come along with it.

Human trials exist and report that it raises GH and IGF-1, with modest lean-mass increases in older adults over months. A large trial in hip-fracture recovery was stopped after congestive heart failure cases in elderly patients. Effects on strength in healthy adults are weakly supported.

• Unusually for this catalog, there are real randomised human trials from its pharmaceutical development. Grading them honestly: GH and IGF-1 elevation is STRONG pharmacodynamic evidence; the fat-free-mass increase in older adults is MODERATE; and meaningful strength, recovery, anti-ageing or physique benefit is NONE SHOWN — FDA's own review concluded the evidence did not establish clinical efficacy for the compounded uses proposed.
• The safety-defining trial was a 123-person phase IIb study in elderly hip-fracture patients — not large, and mostly negative on function (IGF-1 rose and gait speed improved; stair-climb power and most functional measures did not). It was terminated over a congestive heart failure signal. That population's frailty means the incidence cannot be extrapolated to younger users, but the signal is serious and is why caution is warranted at any age. Note the programme's end was not the end of development: ibutamoren was relicensed as LUM-201 and remains investigational in paediatric GH deficiency.
• It also raised fasting glucose and reduced insulin sensitivity in trials — a measured metabolic cost, not a theoretical one.
• What no trial supports is the physique-and-recovery use it is actually sold for. Fat-free mass increased in older adults but strength and function did not, and oedema and weight gain occurred alongside — so how much of the composition change means anything is uncertain. "Raises IGF-1 on a blood test" is not the outcome being marketed.

Orally bioavailable with a half-life around 24 hours, so once-daily exposure sustains elevated GH pulses and IGF-1. The GH rise is pulsatile (it amplifies the body's own rhythm rather than flooding the system), which is the pharmacological argument for it over injected GH — but the elevated IGF-1 is continuous, and that is where the long-term questions sit.

Trial-documented: increased appetite (ghrelin mimicry — often dramatic), water retention, elevated fasting glucose and reduced insulin sensitivity — a meaningful concern for anyone with metabolic goals — plus the cardiac-failure signal in elderly trial populations. Long-term elevation of IGF-1 carries theoretical growth-promotion concerns that trials are too short to resolve.

• Anyone with diabetes, prediabetes or metabolic syndrome — the glucose and insulin-sensitivity effects run directly against that.
• Anyone with heart failure, fluid-retention issues or significant cardiovascular disease, given the fracture-trial signal.
• Anyone with active cancer or high cancer risk — sustained IGF-1 elevation is a theoretical growth-promotion concern trials are too short to resolve.
• Anyone pregnant or breastfeeding — no reproductive safety data exists.
• Children, outside a clinical trial — FDA warned after finding undeclared ibutamoren in a product promoted for children.
• Anyone expecting the marketed anti-aging or recovery outcomes, which the human evidence does not support.

• Insulin and diabetes medication — MK-677 pushes glucose up and insulin sensitivity down, so glycemic control can shift against the drugs managing it.
• Anything else raising GH/IGF-1 (injected GH, secretagogue peptides like ipamorelin/CJC-1295) stacks the same axis and the same fluid and glucose effects.
• It raises cortisol modestly in some data — worth knowing alongside other stress-axis compounds.

• Fasting glucose and HbA1c — the reduced insulin sensitivity is documented and matters for anyone with metabolic risk.
• IGF-1 — the marker the effect runs through; sustained elevation is the thing whose long-term safety is unknown.
• Signs of fluid overload — swelling, breathlessness, rapid weight gain — given the heart-failure signal in the fracture trial.
• Blood pressure, and carpal-tunnel-type symptoms (numbness, tingling) which track GH-mediated fluid retention.

GH and IGF-1 drift back toward baseline after stopping. Beyond that, honesty requires saying the post-discontinuation time course has not been characterised — the trials were not designed to establish what reverses, how fast, or whether prolonged non-medical use leaves endocrine or metabolic sequelae. It does not suppress the hormonal axis the way steroids do, which is a real difference, not a guarantee.

US: not FDA-approved, and FDA has determined ibutamoren is excluded from the dietary-supplement definition because of prior substantial drug investigations — products sold as supplements may be unapproved, misbranded drugs. WADA-prohibited. FDA has also warned after finding undeclared ibutamoren in a product promoted for children.

Papers about this compound, not proof of the claims above. A title says what was studied, which is sometimes a negative result or a different question entirely.

• MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study
  Arch Gerontol Geriatr, 2011
• Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial
  Neurology, 2008
• Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children
  Clin Pharmacol Ther, 2001

• MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolismJ Clin Endocrinol Metab · 1998
• Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping controlRapid Commun Mass Spectrom · 2022
• Characterization of equine liver microsome-generated metabolites of growth hormone secretagogue small molecule ibutamorenRapid Commun Mass Spectrom · 2021
• Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamorenNat Commun · 2021
• The Safety and Efficacy of Growth Hormone SecretagoguesSex Med Rev · 2018
• Antiviral activity of sertindole, raloxifene and ibutamoren against transcription and replication-competent Ebola virus-like particlesBMB Rep · 2020
• Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal malesTransl Androl Urol · 2020
• Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient childrenClin Pharmacol Ther · 2001
• Investigating the P53-dependent anti-cancer effect of ibutamoren in human cancer cell linesBasic Clin Pharmacol Toxicol · 2025
• Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogueClin Chim Acta · 2026
• LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case reportExp Physiol · 2022
• MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb studyArch Gerontol Geriatr · 2011