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Medical notice — For research and educational purposes only. Not medical advice. Consult a licensed physician before using any peptide or compound.

MK-677

gh-releasemuscleappetite
Regulatory status — Research use only — not approved for human use

MK-677 (ibutamoren) is an orally active, non-peptide ghrelin receptor agonist that stimulates pulsatile growth hormone secretion and elevates IGF-1 levels. In two double-blind RCTs in healthy older adults and postmenopausal women, it demonstrated effects on fat-free mass, abdominal visceral fat, and bone turnover markers at 25 mg daily. Case reports document hepatotoxicity, gynecomastia, hypogonadotropic hypogonadism, and dyslipidemia, particularly when combined with SARMs.

Evidence coverage

50/62 claims verified by independent fact-checker.

6 claims pending coverage
  • Source attribution gap(4 claims)
  • No inline citation. Every substantive claim requires a citation per editorial standard. This aggregate count claim has no [src:UUID] attached.(1 claim)
  • Evidence tier below threshold(1 claim)

Pepteligence regenerates entries quarterly and when new high-tier evidence appears.

Quick facts

Half-life
—
Typical dose
25mg/day PO
Route
oral
Frequency
Once daily, based on human RCT protocols [2] [3].
Cycle length
8w-2y
Evidence strength
Phase III RCTs

Suggested labs for this peptide class — educational reference only; not medical advice.

TL;DR

  • Half-life: — — dosed —.
  • Administered via oral.
  • Evidence base: randomised controlled trials.
  • Primary goals: gh-release, muscle, appetite.
EVIDENCE HIERARCHYRCTsObservationalAnimal studiesAnecdotal

Randomised controlled trials

How we evaluate evidence →

How it works

GHRH analogues stimulate pulsatile GH release from the pituitary, elevating IGF-1 and promoting fat oxidation.

MK-677 acts as a ghrelin receptor (GHS-R1a) agonist, binding the receptor with an affinity of 6.5 nM and activating multiple signal transduction systems [1]. Mechanistic data indicate that nonpeptide growth hormone secretagogues such as MK-677 can function both as simple receptor agonists and as positive or negative allosteric modulators of ghrelin signaling at the same receptor [1]. Animal studies indicate that MK-677 and related secretagogues share an overlapping binding site with endogenous ghrelin on the ghrelin receptor [10]. In vitro mechanistic work further characterizes growth hormone secretagogues as orthosteric super-agonists rather than allosteric regulators for activation of the G protein Gα(o1) by the ghrelin receptor [11]. GHS-R1a expression has been identified in the brain and kidney, and animal studies suggest that receptor underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension [12]. Animal studies indicate that oral MK-677 at 4 mg/kg in rats increased peak serum GH, body weight, tibia length, epiphyseal plate width, and IGF-I, consistent with its downstream GH-stimulating mechanism [13]. Preliminary animal data also suggest that ghrelin receptor agonism can reverse stress-induced suppression of food-seeking behavior in fasted mice, pointing to central appetite-related effects of the receptor pathway [14].

What the research says

Research summary content coming soon. Check the references section for indexed studies.

100%50%25%0%00h1t½0h2t½0h3t½0h4t½0h
Approximate plasma concentration over 4 half-lives (0h × 4 = 0h)

Protocol lifecycle

BeforeDuringAfter

Before — Pre-cycle readiness

Readiness checklist

Health status
  • No active liver disease or elevated baseline transaminases
  • No prior gynecomastia or known hormonal dysregulation
  • No active use of hepatotoxic medications or SARM compounds
  • Understand that MK-677 is a research-only compound with no approved clinical indication
Baseline labs
  • Liver function tests (ALT, AST, bilirubin, ALP)
  • Fasting lipid panel (LDL, HDL, triglycerides)
  • Total and free testosterone, LH, FSH
  • IGF-1 (optional; to contextualize any GH-axis effects)
Risk awareness
  • Aware of documented hepatotoxicity signal from case reports [5]
  • Aware of gynecomastia and hypogonadism risk, particularly with SARM co-administration [6]
  • Aware that no efficacy data support use in healthy younger adults for muscle gain or athletic performance
  • Aware that MK-677 is detectable in hair for at least 4 weeks after a single dose [8]
  • Obtain baseline liver function tests (ALT, AST, bilirubin) given hepatotoxicity signals from case reports [5]
  • Obtain baseline lipid panel and testosterone given documented dyslipidemia and hypogonadism signals with combined use [7] [6]
  • Evaluate for contraindications including active liver disease or use of hepatotoxic agents
  • Note: MK-677 is research-only; no approved clinical protocol exists

During — Active protocol

Protocol notice — The following describes common protocols reported in research and community sources. This is not medical advice. Dosing, frequency, and duration should be determined with a licensed physician familiar with peptide research.
  • Human RCTs used 25 mg once daily orally [2] [3]
  • Monitor for edema, increased appetite, and musculoskeletal discomfort as documented side effects [5]
  • Periodic liver function and lipid monitoring is prudent given case-report safety signals [5] [7]
  • Avoid combination with SARMs (e.g., LGD-4033, RAD-140) given compounded safety signals from case reports [7] [6]
  • Be aware that MK-677 is detectable in hair for at least 4 weeks after a single 10 mg dose [8]

After — Post-cycle

  • No evidence-based post-cycle protocol exists in the research packet
  • Recheck liver function tests, lipids, and testosterone after discontinuation, particularly if side effects were observed during use [5] [6]
  • Case report data suggest hepatotoxicity and hormonal disruption may be reversible upon discontinuation, but this is not established from controlled data [5] [6]

Stacks it appears in

MK-677 + LGD-4033 (case report only; combination negatively impacted serum lipids, liver enzymes, and testosterone) [src:5f31583d-0bee-44a7-9212-37df873f1fba]
MK-677LGD-4033 (case report only; combination negatively impacted serum lipids, liver enzymes, and testosterone) [src:5f31583d-0bee-44a7-9212-37df873f1fba]
gh-release
MK-677 + RAD-140 (case report only; combination associated with gynecomastia and hypogonadotropic hypogonadism) [src:509bffe3-cba6-4511-8eb0-4f88bcdd52f0]
MK-677RAD-140 (case report only; combination associated with gynecomastia and hypogonadotropic hypogonadism) [src:509bffe3-cba6-4511-8eb0-4f88bcdd52f0]
gh-release
MK-677 + Alendronate (studied in combination in a postmenopausal osteoporosis RCT) [src:ff5fd723-a9ec-4056-bb34-90184e721bdc]
MK-677Alendronate (studied in combination in a postmenopausal osteoporosis RCT) [src:ff5fd723-a9ec-4056-bb34-90184e721bdc]
gh-release

Related peptides

Other compounds indexed on Pepteligence that share research tags with MK-677. Educational context only.

CJC-1295

Tier 3
gh-releasemuscle

Hexarelin

Tier 3
gh-release

Ipamorelin

Tier 2
gh-release

Sermorelin

Tier 3
gh-release

Safety

Common side effects

  • ·Increased appetite [5]
  • ·Edema [5]
  • ·Muscle pain [5]
  • ·Altered GH isoform composition with disproportionate non-22 kDa GH isoforms, particularly early in administration [9]

Rare side effects

  • ·Gynecomastia (documented in case report; confounding by co-administered RAD-140 cannot be excluded) [6]
  • ·Hypogonadotropic hypogonadism (documented in case report with combined supplement use) [6]
  • ·Dyslipidemia (documented in case report of combined LGD-4033 and MK-677 use) [7]
Safety notice — Serious / theoretical risks:
  • Hepatotoxicity (transaminitis): documented in a case report of a healthy male after approximately 2 months of use; liver function tests normalized after discontinuation [5]
  • Suppressed testosterone and gonadotropins (LH, FSH): documented in case report with combined SARM use; clinical significance when used alone is unknown [7] [6]

Contraindications

  • ·Active liver disease or significantly elevated baseline transaminases (hepatotoxicity case report) [5]
  • ·Known or suspected hormone-sensitive conditions (gynecomastia and hypogonadotropic hypogonadism documented in case reports) [6]
  • ·Concurrent use of SARMs (compounded hepatotoxic and endocrine safety signals from case reports) [7] [6]
  • ·Competitive athletes subject to anti-doping testing (MK-677 is detectable in hair at least 4 weeks after a single 10 mg dose) [8]
  • ·Alzheimer's disease (a 12-month, multicenter RCT of 563 patients found no clinical benefit) [4]

Community experiences

Community content — User-submitted experiences are self-reported and have not been verified. They do not constitute medical advice. Pepteligence aggregates community data under Section 230 protections.

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MK-677 — at a glance

PropertyMK-677—
Half-life——
Routeoral—
Typical dose25mg/day PO—
MechanismMK-677 acts as a ghrelin receptor (GHS-R1a) agonist, binding the receptor with an affinity of 6.5 nM and activating multiple signal transduction systems. Mechanistic data indicate that nonpeptide growth hormone secretagogues such as MK-677 can function both as simple receptor agonists and as positive or negative allosteric modulators of ghrelin signaling at the same receptor. Animal studies indicate that MK-677 and related secretagogues share an overlapping binding site with endogenous ghrelin on the ghrelin receptor. In vitro mechanistic work further characterizes growth hormone secretagogues as orthosteric super-agonists rather than allosteric regulators for activation of the G protein Gα(o1) by the ghrelin receptor. GHS-R1a expression has been identified in the brain and kidney, and animal studies suggest that receptor underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension. Animal studies indicate that oral MK-677 at 4 mg/kg in rats increased peak serum GH, body weight, tibia length, epiphyseal plate width, and IGF-I, consistent with its downstream GH-stimulating mechanism. Preliminary animal data also suggest that ghrelin receptor agonism can reverse stress-induced suppression of food-seeking behavior in fasted mice, pointing to central appetite-related effects of the receptor pathway.—
Evidence strengthrctanecdotal
Primary goalgh-release—

Frequently asked questions

What is MK-677?
MK-677 (also called ibutamoren) is an orally active, non-peptide ghrelin receptor (GHS-R1a) agonist that stimulates pulsatile growth hormone secretion and elevates IGF-1 levels. It is not FDA-approved and is classified as a research compound despite having human RCT data.
How does MK-677 work?
MK-677 binds the ghrelin receptor (GHS-R1a) with an affinity of 6.5 nM and activates multiple signal transduction systems. Research indicates that non-peptide growth hormone secretagogues such as MK-677 can function both as simple receptor agonists and as positive or negative allosteric modulators of ghrelin signaling at the same receptor.
What is MK-677 used for?
Human RCT data in healthy older adults and postmenopausal women have examined effects on fat-free mass, abdominal visceral fat, and bone metabolism. An RCT also studied MK-677 combined with alendronate for osteoporosis outcomes. These are research findings, not approved indications.
Is MK-677 FDA-approved?
No. Despite having human RCT data, MK-677 is not FDA-approved for any indication. It has not completed the regulatory approval process required for clinical use in the United States.
What is the typical dosage of MK-677?
Human RCT protocols have used 25 mg once daily orally. This is the dose documented in the research base — it is not a medically approved therapeutic dose, and dosing outside of a research context has not been validated.
How is MK-677 administered?
MK-677 is taken orally as a once-daily dose, based on human RCT protocols. Its oral bioavailability is a key characteristic that distinguishes it from peptide-based growth hormone secretagogues such as ipamorelin, which require injection.
How long should an MK-677 cycle be?
Human RCT data document use ranging from 8 weeks to approximately 2 years in study protocols. No clinically approved cycle length exists. Duration should be considered carefully in light of the documented safety signals, including hepatotoxicity case reports.
What are common side effects of MK-677?
As a ghrelin receptor agonist, MK-677 can significantly stimulate appetite — increased hunger is among the most consistently reported effects in both research and community settings, consistent with ghrelin's role in appetite regulation.
Are there serious safety concerns with MK-677?
A case report documents hepatotoxicity (liver toxicity) associated with MK-677 use. Use is therefore not advised in people with active liver disease or significantly elevated baseline transaminases. Case reports also associate MK-677 combined with SARMs with negative impacts on serum lipids, liver enzymes, testosterone, and gynecomastia.
Is it safe to combine MK-677 with SARMs?
Case reports document negative outcomes with MK-677 combined with LGD-4033 (impact on serum lipids, liver enzymes, and testosterone) and with RAD-140 (gynecomastia and hypogonadotropic hypogonadism). These are the only available data on these combinations — controlled evidence is absent and the documented signals are concerning.
Is MK-677 legal?
MK-677 is not a scheduled controlled substance in the United States but is not FDA-approved for human use. It occupies a research-compound status. Legal status for possession and sale varies by country and jurisdiction. This is not legal advice — consult applicable regulations in your jurisdiction.
How does MK-677 differ from ipamorelin?
MK-677 is a non-peptide, orally active ghrelin receptor agonist with RCT data spanning up to approximately 2 years. Ipamorelin is a peptide-based GHS administered parenterally with more limited human clinical data. Both stimulate GH release via the ghrelin receptor but differ in chemical structure, route of administration, and available evidence base.

References

  1. [1]

    Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling.

    Holst Birgitte, Brandt Erik, Bach Anders et al.

    Molecular endocrinology (Baltimore, Md.) · 2005 · PMID 15905359

    View on PubMed →
  2. [2]

    Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.

    Nass Ralf, Pezzoli Suzan S, Oliveri Mary Clancy et al.

    Annals of internal medicine · 2008 · PMID 18981485

    View on PubMed →
  3. [3]

    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.

    Murphy M G, Weiss S, McClung M et al.

    The Journal of clinical endocrinology and metabolism · 2001 · PMID 11238495

    View on PubMed →
  4. [4]

    Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.

    Sevigny J J, Ryan J M, van Dyck C H et al.

    Neurology · 2008 · PMID 19015485

    View on PubMed →
  5. [5]

    Hepatotoxicity induced by MK-677.

    Cobani Era, Amin Md Shahnoor, Hasso Muneer et al.

    BMJ case reports · 2025 · PMID 40675653

    View on PubMed →
  6. [6]

    Reversible Gynecomastia and Hypogonadism Due to Usage of Commercial Performance-Enhancing Supplement Use.

    Chong Serena, Woolnough Catherine A, Koyyalamudi Sundar R et al.

    JCEM case reports · 2024 · PMID 39145153

    View on PubMed →
  7. [7]

    LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.

    Cardaci Thomas D, Machek Steven B, Wilburn Dylan T et al.

    Experimental physiology · 2022 · PMID 36303408

    View on PubMed →
  8. [8]

    Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue.

    Kintz Pascal, Gheddar Laurie

    Clinica chimica acta; international journal of clinical chemistry · 2026 · PMID 40882886

    View on PubMed →
  9. [9]

    The effect of treatment with the oral growth hormone (GH) secretagogue MK-677 on GH isoforms.

    Svensson J, Boguszewski C L, Shibata F et al.

    Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2003 · PMID 12550076

    View on PubMed →
  10. [10]

    Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor.

    Holst Birgitte, Frimurer Thomas M, Mokrosinski Jacek et al.

    Molecular pharmacology · 2009 · PMID 18923064

    View on PubMed →
  11. [11]

    Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor.

    Bennett Kirstie A, Langmead Christopher J, Wise Alan et al.

    Molecular pharmacology · 2009 · PMID 19625579

    View on PubMed →
  12. [12]

    Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.

    Sales da Silva Elder, Ferreira Patrícia Maria, Castro Carlos Henrique et al.

    Molecular and cellular endocrinology · 2020 · PMID 32814069

    View on PubMed →
  13. [13]

    Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats.

    Lee Junghun, Kwon Ahreum, Chae Hyun Wook et al.

    Yonsei medical journal · 2018 · PMID 30450851

    View on PubMed →
  14. [14]

    Acute stress suppresses hunger-driven food seeking through PVN activation: Reversal by anxiolytic drug and ghrelin receptor agonist, with anxiolytic-like effects of refeeding.

    Tojo Ryusei, Tashiro Mayuka, Takahashi Haruka et al.

    Neuroscience research · 2026 · PMID 41260416

    View on PubMed →