The oral ghrelin mimetic that amplifies your own growth hormone
Oral · 503A Compounding
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.
Researched and maintained by the PepHookup team. Regulatory status last verified April 17, 2026.
In a controlled crossover study using a hypocaloric diet, 25 mg daily reversed diet-induced protein breakdown, shifting volunteers from negative to roughly neutral nitrogen balance (p < 0.01), the rationale for studying it in muscle-wasting states.[4]
Mimics the physiologic nocturnal ghrelin and GH pulse. A controlled polysomnography study reported increases in REM sleep in young subjects and in stage IV (deep) sleep in older subjects with once-daily oral dosing.[7]
Ibutamoren (development codes MK-677, MK-0677, L-163,191) is a non-peptide, orally active growth hormone secretagogue that acts 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, and the clinically studied form is the mesylate salt. Although it is marketed alongside peptides in the wellness space, it is structurally not a peptide, which is precisely what makes it stable when swallowed.
The compound was discovered and developed by Merck Research Laboratories in the mid-1990s as an orally active successor to earlier injectable growth-hormone-releasing peptides, first characterized in a 1995 PNAS report. It advanced through human studies for sarcopenia and age-related functional decline, hip-fracture recovery, catabolic states, and Alzheimer's disease before Merck stopped development. Its defining pharmacology is an elimination half-life near 24 hours, a time to peak concentration of roughly 2 to 3 hours, and a profile that preserves natural GH pulsatility while largely sparing cortisol.
Ibutamoren is not FDA-approved for any indication. In the United States it sits in a regulatory gray zone for compounding, and a licensed provider determines whether it is appropriate for a given person along with any dose. The clinical record below is a mix of well-conducted human randomized trials and supporting mechanistic and animal work, and the prose distinguishes the two.
Ibutamoren binds and activates GHSR-1a on somatotrophs of the anterior pituitary and on hypothalamic neurons, imitating endogenous ghrelin. GHSR-1a is a Gq-coupled G-protein-coupled receptor, so activation drives phospholipase-C and IP3 signaling, intracellular calcium release, and pulsatile GH secretion. Unlike injected recombinant GH, which blunts the body's own pulses through negative feedback, ibutamoren amplifies native pulse amplitude, which in turn raises hepatic IGF-1 production.
Elevated GH and IGF-1 promote nitrogen retention, protein synthesis, lipolysis, and bone remodeling. In the Nass trial, GH and IGF-1 in adults aged 60 to 81 rose into the range typical of healthy young adults, and fat-free mass increased. Reported secondary effects across the trial program include higher bone-turnover markers, a modest decline in insulin sensitivity with small rises in fasting glucose and HbA1c, small increases in prolactin, and fluid retention characteristic of GH action.
Because the half-life is near 24 hours and the drug amplifies the nighttime physiologic GH pulse, most studies used a single daily oral dose, often at bedtime. That pharmacology is the basis for its reported sleep effects and for the common evening-dosing protocol. Importantly, ibutamoren does not replace GH. It needs an intact pituitary reserve to work, which is why it performs best where the axis is blunted but functional, such as healthy aging, and why it failed to alter disease course in Alzheimer's despite raising IGF-1.
The oral ghrelin mimetic that amplifies your own growth hormone
Ibutamoren is an oral ghrelin-receptor agonist that amplifies the body's own growth hormone pulses, raising IGF-1 toward the young-adult range while keeping the pituitary feedback loop in play rather than overriding it.
25 mg/day increased fat-free mass by +1.1 kg versus -0.5 kg on placebo (p < 0.001) and raised GH and IGF-1 to young-adult levels. Body weight rose modestly. Strength and functional endpoints did not significantly improve, and the trial was not powered to assess them definitively.
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
On a hypocaloric diet, 25 mg/day shifted nitrogen balance from -1.48 g/day on placebo to +0.31 g/day on MK-677 (p < 0.01), reversing diet-induced protein loss. This is the basis for interest in catabolic and muscle-wasting states.
Murphy MG, Plunkett LM, Gertz BJ, He W, Wittreich J, Polvino WM, Clemmons DR · J Clin Endocrinol Metab, 83(2):320-325 (1998) · PubMed
25 mg/day for 8 weeks increased GH secretion, raised IGF-1 by about 40%, and increased fat-free mass and resting energy expenditure. Total and visceral fat did not change significantly over this short window.
Svensson J, Lonn L, Jansson JO, Murphy G, Wyss D, Krupa D, Cerchio K, Polvino W, Gertz B, Boseaus I, Sjostrom L, Bengtsson BA · J Clin Endocrinol Metab, 83(2):362-369 (1998) · PubMed
Gait speed improved (p = 0.011) and IGF-1 rose by about 51 ng/mL (p < 0.001), but the stair-climbing-power primary endpoint was not met. The trial was stopped early after a congestive heart failure imbalance (4 of 62, 6.5%, vs 1 of 61, 1.7%), and the authors judged the safety profile unfavorable in this frail population.
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
IGF-1 rose about 60% at 6 weeks and about 73% at 12 months, confirming target engagement, but there was no benefit on ADAS-Cog, CIBIC-plus, ADCS-ADL, or CDR-sob versus placebo. A clear illustration that raising IGF-1 does not by itself change every disease.
Sevigny JJ, Ryan JM, van Dyck CH, Peng Y, Lines CR, Nessly ML · Neurology, 71(21):1702-1708 (2008) · PubMed
start low, go slow
Oral
Oral (lower-dose introductory)
Oral: The most-studied dose (Nass 2008, Adunsky 2011, Sevigny 2008, Svensson 1998, Murphy 1998). Produces the strongest IGF-1 response, and also the most pronounced appetite, fluid retention, and glucose shifts.
Oral (lower-dose introductory): Aligns with the lower arms of the Chapman 1996 dose-ranging study (2, 10, 25 mg). Often chosen first for people sensitive to edema, appetite, or lethargy before any up-titration.
Dosing is determined by a licensed provider based on the individual's goals, metabolic health, and tolerance. Published human doses range from 2 to 25 mg/day, with 25 mg the most-studied and also the most side-effect prone.
Evening dosing aligns with the nocturnal physiologic GH pulse and is the regimen used in the sleep-architecture work.
Baseline and periodic fasting glucose, HbA1c, and IGF-1 are reasonable to track. IGF-1 typically rises within about 2 weeks and plateaus by 4 to 8 weeks.
Track fasting glucose, HbA1c, and insulin sensitivity at baseline and periodically. Use is generally avoided in uncontrolled type 2 diabetes given GH-mediated insulin resistance.
Because IGF-1 is mitogenic, it is generally avoided in active or suspected malignancy, and the long-term cancer implications of sustained IGF-1 elevation are unresolved.
Caution is warranted in older or frail patients with cardiovascular disease. The Adunsky 2011 hip-fracture trial was halted early for a congestive heart failure imbalance, and fluid retention can precipitate cardiac decompensation in vulnerable people.
Ibutamoren is not FDA-approved as a drug, and long-term human safety data beyond trial periods are limited.
| Peptide | Primary Use | Administration | Cycle Length | Key Differentiator |
|---|---|---|---|---|
| Ibutamoren (MK-677) | Anti-Aging & Body Composition | Oral | 8 to 16 weeks typical | The only well-studied orally active ghrelin-receptor agonist, delivering sustained 24-hour IGF-1 elevation without injections, unlike peptide secretagogues such as CJC-1295 or ipamorelin. |
| SS-31 (Elamipretide) | Mitochondrial restoration and rare mitochondrial disease | Subcutaneous injection (daily); IV in trials | Ongoing daily dosing | The first FDA-approved mitochondria-targeted therapeutic; binds cardiolipin on the inner mitochondrial membrane to support electron transport efficiency |
| Tesamorelin | Visceral Fat & GHRH Signaling | Subcutaneous Injection | Ongoing daily | The only FDA-approved GHRH analog, with Phase III data in over 800 patients, documented liver-fat reduction, and physiologic pulsatile GH release |
| GHK-Cu | Anti-Aging & Skin Regeneration | Topical, Injection | 8-12 weeks | A naturally occurring copper-carrier peptide that rebuilds the skin matrix and, per gene-expression analysis, shifts expression of about a third of human genes toward repair |
| Sermorelin | GH restoration and healthy aging | Subcutaneous injection, daily at bedtime | 3-6 months | The GHRH analog with prior FDA approval and a multi-decade clinical record, preserving natural feedback rather than replacing growth hormone |
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)
Svensson J, Lonn L, Jansson JO, Murphy G, Wyss D, Krupa D, Cerchio K, Polvino W, Gertz B, Boseaus I, Sjostrom L, Bengtsson BA “Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.” J Clin Endocrinol Metab, 83(2):362-369 (1998)
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)
Looking into Ibutamoren (MK-677)? Find a provider who knows this peptide and can walk you through your options.
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