MK-677

MK-677 (ibutamoren) is a non-peptide spiropiperidine designed by Merck as an orally bioavailable agonist of the growth-hormone-secretagogue receptor — the ghrelin receptor, GHSR-1a — on pituitary somatotrophs ([Nass et al., *Ann Intern Med* 2008, 149:601–611](https://doi.org/10.7326/0003-4819-149-9-200811040-00003)). Receptor agonism triggers pulsatile growth hormone release in the same downstream pathway as Ipamorelin, with the practical advantage that it is absorbed orally and clears with a half-life that supports once-daily dosing. Strictly speaking, MK-677 is not a peptide — it is a small molecule that mimics ghrelin's receptor activity. This site labels it "peptide-adjacent" because the GH-axis function it serves is the same one biohackers approach via the injectable peptides on this list, and excluding it would make the GH-secretagogue conversation less complete than it should be.

MK-677 is the GH-secretagogue most biohackers actually try, and the entry point for everyone who wants the GH-axis story without the injection logistics. The orally active design is the headline; the human evidence base is also unusually deep for this corpus. The Nass 2008 trial in *Annals of Internal Medicine* randomized 65 healthy adults aged 60–81 to 25 mg daily MK-677 or placebo for two years in a modified-crossover design, with a primary focus on body composition and clinical outcomes. The trial is the cleanest source on this site for what daily ghrelin-mimetic dosing actually does in humans. The findings sit in tension with the marketing story. MK-677 raised GH and IGF-1 to young-adult levels and increased fat-free mass by 1.1 kg over the first year (versus a 0.5 kg loss on placebo). Body weight rose by 2.7 kg, with most of the gain in fat-free mass and limb fat. But the increased fat-free mass *did not translate into measurable strength or functional improvements*. Fasting glucose rose modestly (+0.3 mmol/L), insulin sensitivity decreased, and cortisol levels increased. Lower-extremity edema was the most common reported side effect during titration; appetite increased (consistent with the ghrelin pathway) and subsided over months. The two-year analyses were exploratory but consistent with the one-year results. Three honest reads emerge from this. First, MK-677 reliably moves the GH-axis numbers in older adults; the mechanism works as designed. Second, the body-composition gains are real but lean-mass gain without strength gain is a subtle outcome — anyone interpreting MK-677 as a clean recomposition tool should weight the strength data more than the scale data. Third, the glycemic signal is small but real and matters for anyone with metabolic risk factors. Cycling, biomarker monitoring, and clinician oversight rather than open-ended self-administration are the practitioner-default frame.