MK-677 / Ibutamoren

Not a peptide. MK-677 (ibutamoren) is an orally active small molecule — a spiroindoline ("spiropiperidine") compound developed by Merck in the 1990s. It is included because it is constantly discussed alongside peptides as an oral alternative to GH secretagogues such as ipamorelin and GHRPs, and people search for it here. The same evidence standards apply.

Ibutamoren, ibutamoren mesylate, MK-0677, L-163,191, Nutrobal (marketing name), Oratrope (historical)

Growth hormone axis

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Non-peptide small-molecule ghrelin receptor (GHS-R1a) agonist; oral
Mechanism: Mimics ghrelin to increase pulsatile growth hormone release and raise IGF-1 around the clock, with a strong appetite effect
Routes studied: Oral, once daily (humans, usually at bedtime in trials)
Dose range reported: Trials: 2–50 mg/day, with 25 mg/day the standard in most studies; 10 mg/day in the older-adult and hip-fracture trials of longer duration. Community: 10–25 mg/day, often at night; higher doses reported with more side effects. No approved dose exists
Half-life: ~4–6 hours for the molecule, but IGF-1 remains elevated for 24 hours with once-daily dosing, and GH pulse amplitude is increased through the night
Storage: Research powders or capsules: room temperature, dry, protected from light; the mesylate salt is stable
Regulatory status: Never approved anywhere; development ended. Sold as an unapproved "research chemical" and the subject of regulatory warnings in several countries

Doses are as reported in studies or by the community — never recommendations.

1What it is

Ibutamoren was Merck's attempt to turn the GHRP discovery into a pill. Working from GHRP-6, Merck chemists designed non-peptide molecules that fit the same receptor, arriving at MK-677 in 1995. It was studied extensively in the late 1990s and 2000s — in healthy young and older adults, obese men, people on calorie restriction, hip-fracture patients, Alzheimer's disease and sleep — producing one of the richest human datasets of any GH . The consistent finding was that it reliably raises GH and IGF-1 and adds a kilogram or two of lean mass, while failing to improve strength, function or disease outcomes and reliably worsening glucose handling. Merck stopped development.

It is one of the most widely used compounds in the fitness community, sold alongside SARMs as "Nutrobal", and it is routinely described as a peptide although it is not one. Because it is oral, long-acting and cheap to make, it has largely displaced injectable GHRPs for people who want IGF-1 elevation without injections.

2How it's thought to work

MK-677 binds in the pituitary and hypothalamus. Rather than producing one sharp GH spike, once-daily dosing amplifies the natural pulses — especially the large nocturnal pulses — so the 24-hour GH profile is raised and IGF-1 climbs over one to two weeks and stays up. Unlike injected GH it does not abolish pulsatility or feedback, which is argued to be safer; the glucose data suggest the metabolic cost is still real. As a ghrelin mimic it also strongly stimulates appetite, raises cortisol slightly and transiently, and has effects on sleep architecture (more deep sleep in the one sleep study). The lean mass gain in trials is partly water: ghrelin receptor activation and GH both cause sodium retention.

An oral small molecule that mimics ghrelin: growth hormone keeps its pulses (bottom) while IGF-1 stays raised day and night (top).Schematic — not to scale

3What the research shows

GH and IGF-1 elevation

In healthy older adults, 2–25 mg/day for 4 weeks raised IGF-1 dose-dependently into the young-adult range and increased GH pulse amplitude (Chapman 1996, JCEM). This is the one thing MK-677 does unambiguously. [1]

Graded A (lean mass yes, function no)

Body composition in older adults

A two-year randomised, double-blind, placebo-controlled trial in 65 healthy adults aged 60–81 (25 mg/day) found fat-free mass increased by ~1.1 kg and IGF-1 rose ~40–50%, with no significant change in strength, physical function or fat mass. Fasting glucose rose ~5 mg/dL, HbA1c rose, and insulin sensitivity fell; more participants reported increased appetite, oedema and muscle pain (Nass 2008, Ann Intern Med). The authors' conclusion was that it was not a therapy for sarcopenia on the evidence. [2]

Graded A (negative for fat loss)

Obesity

In 24 obese men, 25 mg/day for 8 weeks increased fat-free mass by ~3 kg and raised IGF-1 ~40%, with no change in total or visceral fat and a rise in fasting glucose and insulin (Svensson 1998, JCEM). It is not a fat-loss compound. [3]

Graded A (small, positive)

Catabolic states

In healthy young men on a severe short-term calorie restriction, 25 mg/day reversed the nitrogen wasting (Murphy 1998, JCEM). In older adults recovering from hip fracture, 25 mg/day for 6 months improved some gait measures but was associated with more congestive heart failure in the treated group, which led to the trial being stopped early (Bach 2004, J Am Geriatr Soc; related Adunsky 2011 report). Treat the heart failure signal as real until shown otherwise. [4][5]

Graded B/A (small)

Sleep

A placebo-controlled crossover study in 8 young and 6 older adults reported increased stage IV (deep) sleep and REM in young subjects and increased REM in older subjects on 25 mg/day for a week (Copinschi 1997, Neuroendocrinology). Small, short, and the basis of the community's sleep claim. [6]

Graded A (markers only)

Bone

Bone formation and resorption markers both rose over 2–9 weeks, consistent with increased turnover; bone density changes were small and not clearly beneficial (Murphy 1999, JCEM; Murphy 2001, JCEM — with alendronate in osteoporotic women). [7]

Graded A (negative)

Alzheimer's disease

A 12-month randomised trial in 563 patients with mild-to-moderate Alzheimer's (25 mg/day) found no effect on cognitive or functional decline despite raised IGF-1 (Sevigny 2008, Neurology). [8]

Community claims: muscle growth in young trainees, injury healing, hair and skin, "anti-ageing"

No trials. The trials that exist were in older, obese or ill populations and found modest lean mass without strength gain.

4Reported side effects and interactions

Literature-reported

Common (literature). increased appetite (near-universal), transient oedema and water retention, muscle and joint pain, raised fasting glucose and HbA1c, reduced insulin sensitivity, lethargy, mild transient cortisol rise, numbness or tingling (carpal-tunnel-like) at higher doses.

Serious (literature). increased congestive heart failure in frail older hip-fracture patients (Bach 2004) — the most important safety signal in the dataset; new-onset glucose intolerance; one trial reported increased blood pressure modestly.

Community-reported

hunger strong enough to drive unwanted weight gain; lethargy and "brain fog" with daytime dosing; water retention and puffiness; vivid dreams; numb or tingling hands; raised fasting glucose on home testing; occasional reports of increased anxiety or lowered mood. Prolactin changes are reported inconsistently.

Theoretical. long-term IGF-1 elevation and cancer risk — epidemiological association exists for IGF-1 in general, and no long-term MK-677 safety data beyond two years exist; effects on existing insulin resistance and pre-diabetes are predictable; no data on use under age 25, where growth plates may still be open in some.

Product quality. regulators (including the FDA in 2017 warning letters covering SARM and MK-677 products) have found mislabelled and contaminated products; testing of "MK-677" supplements has repeatedly found wrong doses or different compounds.

Interactions. glucose-lowering medicines and insulin (opposing effect on glucose); additive with injectable GH and GH; CYP3A4 inhibitors may raise exposure †; caution with any drug or condition predisposing to fluid overload.

Markers researchers commonly monitor

Better founded than for most compounds in this category because the trials measured them:

Marker	Why it's watched
IGF-1	rose 40–90% in trials; the marker of effect, and the main lever for choosing a dose. Values above the age-adjusted range are the over-exposure signal.
Fasting glucose, fasting insulin, HbA1c	rose in every trial that measured them; the most important safety markers. An oral glucose tolerance test or HOMA-IR adds sensitivity.
Blood pressure, morning body weight, ankle oedema	fluid retention and the heart failure signal.
Lipid panel	GH shifts lipids; LDL fell slightly in some trials.
Morning cortisol	small transient rises documented; usually clinically trivial but worth a baseline.
Prolactin	community concern, inconsistent evidence; a baseline settles it.
Body composition (DEXA) and grip strength	the trials showed lean mass without strength; tracking both keeps expectations honest.
Sleep log or wearable	to test the sleep claim for oneself.

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

Sold as powder, capsules (commonly 10–25 mg) or liquid "research" solutions, none to pharmaceutical standards. Store at room temperature, dry and dark. Doses are in milligrams, so accurate dosing from bulk powder requires a milligram balance. Trials dosed once daily, usually at bedtime; community dosing follows that. No calculator link is offered.

6Commonly studied alongside

In trials: alendronate (bone), nothing else. In the community: SARMs (common and entirely untested together), ipamorelin and CJC-1295 / mod GRF 1-29 (redundant in mechanism for the GHRP part), GH / somatropin (which suppresses the endogenous axis MK-677 acts on), GLP-1 agonists (to counter appetite — no data). Capromorelin and anamorelin are the closest pharmacological relatives.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; not a dietary supplement ingredient and the FDA has issued warning letters to sellers marketing it as one; not a controlled substance as of review date †
European Union	Not authorised; several national agencies have issued warnings about products containing it
United Kingdom	Not licensed; MHRA has acted against sellers marketing it as a supplement †
Australia	Prescription-only (Schedule 4) — the TGA scheduled ibutamoren alongside SARMs, making unprescribed import and supply illegal †
South Africa	Not registered
Sport	Prohibited by WADA (S2 — ibutamoren is named as an example of a GH secretagogue); multiple positive tests in professional sport

8Open questions

Long-term (beyond two years) safety, particularly cancer risk and cardiac effects.
Whether the heart failure signal in frail elderly applies to healthy younger adults.
Whether cycling, lower doses or co-use with anything mitigates the glucose effect — untested.
Any functional benefit at all in the populations that actually use it; no trial has looked.

9References

1Chapman IM et al. (1996). 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. PubMed · DOI
2Nass R et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. PubMed · DOI
3Svensson J et al. (1998). 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. PubMed · DOI
4Murphy MG et al. (1998). MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. PubMed · DOI
5Bach MA et al. (2004). The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. PubMed · DOI
6Copinschi G et al. (1997). Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology. PubMed · DOI
7Murphy MG et al. (2001). 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. PubMed · DOI
8Sevigny JJ et al. (2008). Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial. Neurology. PubMed · DOI
9Patchett AA et al. (1995). Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue. Proc Natl Acad Sci USA. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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