The oral ghrelin mimetic that amplifies your own GH
An orally active ghrelin receptor agonist that elevates growth hormone and IGF-1.
Educational content. This page describes Ibutamoren (MK-677) for informational purposes only and is not medical advice, diagnosis, or treatment. Consult a licensed provider before starting, stopping, or modifying any therapy.
In a 2-year randomized trial, 25 mg/day increased fat-free mass by approximately 1.1 kg versus a 0.5 kg loss on placebo (p < 0.001), consistent with GH/IGF-1 driven anabolism.[1]
Ibutamoren (development codes MK-677, MK-0677, L-163,191) is a non-peptide, orally active growth hormone secretagogue that functions as a potent, selective agonist of the growth hormone secretagogue receptor type 1a (GHSR-1a), better known as the ghrelin receptor. Chemically it is a spiropiperidine small molecule (free base C27H36N4O5S, MW 528.67 g/mol; the clinically studied mesylate salt has MW 624.77 g/mol). Despite being grouped with peptides in wellness marketing, it is structurally non-peptidic, which is what makes it orally stable.
The compound was discovered and developed by Merck Research Laboratories in the mid-1990s (Patchett et al., PNAS 1995) as an oral successor to earlier injectable growth hormone releasing peptides. It advanced through Phase II trials for sarcopenia, age-related functional decline, hip-fracture recovery, pediatric growth hormone deficiency, and Alzheimer's disease before Merck halted development. Distinguishing properties include an elimination half-life of approximately 24 hours, Tmax of 2–3 hours, and a pharmacologic profile that preserves GH pulsatility while largely sparing cortisol and producing only small effects on prolactin at therapeutic doses.
Ibutamoren binds and activates GHSR-1a on somatotrophs of the anterior pituitary and on hypothalamic neurons, mimicking endogenous ghrelin. GHSR-1a is a Gq-coupled G-protein coupled receptor; activation triggers phospholipase-C/IP3 signaling, intracellular calcium release, and pulsatile GH secretion. Unlike exogenous recombinant GH, which blunts physiological pulses, ibutamoren amplifies native pulse amplitude and frequency, driving downstream hepatic IGF-1 synthesis.
Elevated GH and IGF-1 drive nitrogen retention, protein synthesis, lipolysis, and bone remodeling. In the Nass trial, GH and IGF-1 in older adults rose into the range typical of healthy young adults. Secondary findings across trials include increased bone turnover markers, modest declines in insulin sensitivity, mild elevations in fasting glucose and HbA1c, small increases in T3 and prolactin, and sodium/water retention characteristic of GH action.
Because ibutamoren has a ~24-hour half-life and amplifies nighttime physiologic GH pulses, most trials used single daily oral dosing, often at bedtime. This pharmacology is the rationale for its reported sleep-quality effects and for the common protocol of evening administration. Ibutamoren does not replace GH. It requires an intact pituitary somatotroph reserve, which is why it performs best in populations where the axis is blunted but not destroyed (e.g., healthy aging).
The oral ghrelin mimetic that amplifies your own GH
Ibutamoren is an oral ghrelin-receptor agonist that amplifies the body's own growth hormone pulses, raising IGF-1 into the young-adult range without bypassing the pituitary feedback loop.
Key studies supporting the therapeutic use of this peptide.
25 mg/day increased fat-free mass by +1.1 kg versus -0.5 kg on placebo (p < 0.001) and restored GH/IGF-1 to young-adult levels. Strength and functional measures did not significantly improve.
Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE Jr, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO — Ann Intern Med, 149(9):601-611 (2008) · PubMed
Gait speed improved modestly (p = 0.011) and IGF-1 rose by ~51 ng/mL (p < 0.001), but the stair-climbing-power primary endpoint did not reach significance. Trial was terminated early after a congestive heart failure safety signal (6.5% vs 1.7%).
Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA — Arch Gerontol Geriatr, 53(2):183-189 (2011) · PubMed
Dose-dependent restoration of 24-hour GH profile and IGF-1 to the young-adult range. The 25 mg dose produced the strongest and most sustained response over 4 weeks.
Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO — J Clin Endocrinol Metab, 81(12):4249-4257 (1996)
IGF-1 rose ~60% at 6 months and ~73% at 12 months, confirming target engagement, but no change in ADAS-Cog, CIBIC-plus, or ADCS-ADL versus placebo.
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML — Neurology, 71(21):1702-1708 (2008) · PubMed
Typical protocols used in clinical practice. Always consult a licensed provider for personalized dosing.
Oral
Oral (Lower-dose introductory)
Oral: The most-studied dose (Nass 2008, Adunsky 2011, Sevigny 2008, Murphy 2001). Produces the strongest IGF-1 response but also the most pronounced appetite, edema, and glucose shifts.
Oral (Lower-dose introductory): Used in the Chapman 1996 lower-dose arm. Often preferred for patients sensitive to edema, appetite, or lethargy before up-titration.
Published human doses fall within 2–25 mg/day. 25 mg is the most-studied dose but produces more pronounced side effects than 10–12.5 mg.
Evening dosing aligns with the nocturnal physiologic GH pulse and is the regimen used in most sleep-architecture reports.
Baseline and serial fasting glucose, HbA1c, and IGF-1 monitoring are appropriate. Effects typically plateau by 4–8 weeks.
Monitor fasting glucose, HbA1c, and insulin sensitivity at baseline and periodically. Avoid use in uncontrolled type 2 diabetes given GH-mediated insulin resistance.
Contraindicated in active or suspected malignancy. IGF-1 is mitogenic, and the long-term oncology signal of sustained IGF-1 elevation is unresolved.
Use caution in elderly or frail patients with cardiovascular comorbidity: the Adunsky 2011 hip-fracture trial was halted early for a congestive heart failure imbalance (6.5% MK-677 vs 1.7% placebo), and fluid retention can precipitate decompensation.
See how Ibutamoren (MK-677) compares to peptides with overlapping benefits.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Ibutamoren (MK-677) | Anti-Aging & Body Composition | Oral | 8–16 weeks typical | The only well-studied orally active ghrelin-receptor agonist. Delivers sustained 24-hour IGF-1 elevation without injections, unlike peptide secretagogues such as CJC-1295 or ipamorelin. |
| SS-31 (Elamipretide) | Mitochondrial Restoration & Anti-Aging | Injection (daily) | Continuous (weeks to months) | Only peptide that directly targets cardiolipin on the inner mitochondrial membrane to restore electron transport chain efficiency |
| Tesamorelin | Body Composition & GHRH | Subcutaneous Injection | Ongoing daily | The only FDA-approved GHRH analog with Phase III data in over 800 patients, proven hepatoprotective effects, and physiologic pulsatile GH release |
| GHK-Cu | Anti-Aging & Recovery | Topical, Injection | 8–12 weeks | Only peptide demonstrated to modulate ~31% of human genes, epigenetically resetting cellular function toward a younger phenotype |
| Sermorelin | Anti-Aging & GH Restoration | Injection (daily) | 3–6 months | Only GHRH analog with FDA approval history and multi-decade safety record, uniquely preserving natural GH feedback |
Current FDA classification and compounding eligibility.
The FDA placed this substance in Category 2 of the 503A bulk drug substances evaluation, flagging significant safety risks. 503A compounding carries FDA enforcement risk, so most pharmacies decline to prepare it and many physicians hesitate to prescribe it.
In April 2026, HHS Secretary Robert F. Kennedy Jr. announced that nominators withdrew 12 peptides from Category 2 of the FDA's 503A bulk drug substances evaluation, including this one. The FDA referred them to its Pharmacy Compounding Advisory Committee (PCAC) for re-evaluation at meetings beginning July 2026. If PCAC recommends Category 1 status and the FDA agrees, licensed 503A pharmacies could compound it under FDA enforcement discretion again. The outcome is not final.
A non-peptide small molecule (despite being marketed alongside peptides in the wellness space). Listed in Category 2 for compounding purposes. Named by HHS in April 2026 among 12 substances withdrawn from Category 2 for PCAC re-evaluation.
FDA PCAC re-evaluation following April 2026 withdrawal from Category 2. Expected Q3 2026 onward.
Listed as 'Ibutamoren Mesylate (MK-677)' in 503A Category 2
Last verified April 17, 2026. PepHookup tracks public FDA actions. This is not legal or medical advice.
Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, Schilling LM, Cole KY, Skiles EH, Pezzoli SS, Hartman ML, Veldhuis JD, Gormley GJ, Thorner MO “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, 81(12):4249-4257 (1996)
Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ “Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women.” J Clin Endocrinol Metab, 86(3):1116-1125 (2001)
Murphy MG, Bach MA, Plotkin D, Bolognese M, Ghigo E, Factor K, Cook B, Petrie LM, Gertz BJ “Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults.” J Bone Miner Res, 14(7):1182-1188 (1999)
Copinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, Mendel CM, De Lepeleire I, Bolognese JA, Van Cauter E “Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.” Neuroendocrinology, 66(4):278-286 (1997)
Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G, et al. “Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.” Proc Natl Acad Sci USA, 92(15):7001-7005 (1995)
Looking into Ibutamoren (MK-677)? Find a provider who knows this peptide and can walk you through your options.
Find a ProviderA mitochondria-targeted tetrapeptide that stabilizes cardiolipin to support cellular energy.
FDA-approved as Forzinity for Barth syndrome in 2025; the first mitochondria-targeted therapeutic approved.
A tripeptide-copper complex that supports skin regeneration and wound healing.
Naturally occurring in plasma; levels decline with age. Widely used in topical and compounded formulations.
A 29-residue GHRH analog that prompts the pituitary to release endogenous growth hormone.
Formerly marketed as Geref for pediatric GH deficiency; discontinued in 2008 for commercial reasons.