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 — because it was developed as a pharmaceutical before being abandoned. They confirm it durably raises GH and IGF-1 and increases lean body mass and appetite.
• The trial that matters most for the safety conversation is the one in older adults with hip fracture: it was halted over an increase in congestive heart failure and fluid-overload signals. That finding, in the population most like long-term users, is the reason development stopped.
• 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; the lean-mass gain is partly water, and "raises IGF-1 on a blood test" is not the same as the body-composition or anti-aging outcomes 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 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 return to baseline after stopping, and with them much of the appetite, water weight and the glucose effects — a good deal of the visible "gains" is in that reversible fraction, which is why people describe a let-down on coming off. It does not suppress your own hormone axis the way steroids do, so there is no distinct recovery syndrome; the main thing that reverses is simply the drug's own effects.

US: not approved, sold as a "research chemical" without oversight. WADA-banned.

• 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