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    Fact-checked by the Peptide Authority Editorial Board · Last reviewed:

    Corrected : The sleep-study summary described the Copinschi et al. (1997) trial as a study in 12 young men. Per the paper's abstract, it enrolled 8 young subjects (18-30 years) plus a separate cohort of 6 older adults; the study details have been rewritten to match.

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    Hormonal & Endocrine•Updated 2026-09-25•8 min read

    What Is MK-677? Benefits, Research & Safety

    A potent, orally active non-peptide growth hormone secretagogue that mimics ghrelin to stimulate sustained GH and IGF-1 elevation, widely researched for body composition, sleep, and bone density.

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    Also known as:
    Ibutamoren
    Ibutamoren Mesylate
    MK-0677
    L-163,191
    Nutrobal
    CLimited human evidenceUK: Unlicensed (UK)WADA: Prohibited in sport

    UK summary: Not a licensed UK medicine and not technically a peptide — MK-677 is an orally active non-peptide ghrelin-receptor agonist / GH secretagogue. Substantial human pharmacology data exists; development stalled in elderly/hip-fracture indications. Prohibited under WADA S2.

    Quick Facts

    Category
    Hormonal & Endocrine
    Half-Life
    Approximately 4-6 hours plasma half-life, but biological effects (IGF-1 elevation) persist for approximately 24 hours due to downstream signalling
    UK Status
    Not a licensed medicine. Not approved by the MHRA. Available as a research chemical. Prohibited by WADA and UK Anti-Doping.
    EU Status
    Not authorised by EMA for human use. Classified as an investigational compound. Banned in competitive sports across all EU member states.

    Overview

    MK-677 (Ibutamoren) is a non-peptide, orally active growth hormone secretagogue (GHS) that stimulates the pituitary gland to release growth hormone by mimicking the action of ghrelin — the endogenous "hunger hormone." Unlike injectable GH peptides such as CJC-1295 or Ipamorelin, MK-677 is taken orally and has a long duration of action, producing sustained elevations in GH and IGF-1 for up to 24 hours per dose. Developed by Merck in the 1990s, MK-677 reached Phase II clinical trials for several indications including growth hormone deficiency, muscle wasting, osteoporosis, and obesity. While it demonstrated clear efficacy in raising GH and IGF-1, concerns about insulin resistance and metabolic side effects prevented it from gaining regulatory approval. MK-677's molecular formula is C27H36N4O5S, with a molecular weight of 528.7 g/mol. It functions as a selective agonist of the growth hormone secretagogue receptor (GHS-R1a), the same receptor targeted by ghrelin. Its oral bioavailability and once-daily dosing made it one of the most popular GH-elevating compounds in the research peptide space. MK-677 is not approved for human therapeutic use by any regulatory authority including the MHRA, EMA, or FDA. It is prohibited by WADA in competitive sports. All information here is for educational purposes based on published research.
    Evidence standards summary

    MK-677 — evidence and risk at a glance

    Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

    01Evidence snapshot

    CLimited human evidenceOverall grade against our evidence grading methodology.

    Not a licensed UK medicine and not technically a peptide — MK-677 is an orally active non-peptide ghrelin-receptor agonist / GH secretagogue. Substantial human pharmacology data exists; development stalled in elderly/hip-fracture indications. Prohibited under WADA S2.

    02Human evidence grade

    CLimited human evidenceStrength of evidence from published human trials.

    03Preclinical evidence grade

    BModerate human evidenceAnimal-model and in-vitro evidence quality.

    04Regulatory status

    • UK: Not a licensed medicine. Not approved by the MHRA. Available as a research chemical. Prohibited by WADA and UK Anti-Doping.
    • EU: Not authorised by EMA for human use. Classified as an investigational compound. Banned in competitive sports across all EU member states.
    • Notes: MK-677 has never received regulatory approval from any major authority (FDA, MHRA, EMA). Despite reaching Phase II trials, Merck discontinued development. It is widely available online as a 'research chemical' or 'SARM' (despite not being a SARM). Its sale for human consumption is illegal in most jurisdictions. WADA classifies it as a prohibited substance under S2 (Peptide Hormones, Growth Factors).

    05Approved medical uses

    None in the UK or EU as a finished medicine. (Or: not yet documented; treat as absence rather than approval.)

    06Unapproved / promotional claims

    • Safe oral alternative to injectable growth hormone
    • Anti-ageing pill that reverses sarcopenia in healthy adults
    • Lean-mass gain without insulin or cardiovascular cost

    07Common internet claims

    • Equivalent to HGH
    • ‘Recovery’ and ‘deep sleep’ supplement with no downside
    • Long-term cycling is well-established and safe

    08Claim vs evidence

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Oral GH boost without injections”BYesHighMK-677 does raise GH and IGF-1 levels in human studies; sustained elevation has tolerability concerns (water retention, insulin resistance, appetite increase).
    “Safe long-term for body composition”CLimitedHighInsulin-resistance, water-retention, and congestive-heart-failure concerns are documented; not a UK-licensed long-term agent.
    “Legal because it's not a peptide / not a steroid”ENoHighProhibited at all times under WADA S2 (GH secretagogues). Sale to consumers without authorisation engages UK medicines law.

    09Safety uncertainty score

    High

    Limited human safety data; meaningful uncertainty about rare or long-term effects.

    10Known adverse signals

    • Insulin resistance and elevated fasting glucose (documented in trials)
    • Water retention, oedema, joint discomfort
    • Congestive heart failure signal in elderly trial subgroups
    • Increased appetite (mechanism — ghrelin-receptor agonism)
    • WADA S2 strict-liability risk for athletes

    11Drug-interaction uncertainty

    Moderate

    Some interaction data published; check with a prescriber for your specific medicines.

    12Anti-doping status

    WADA: Prohibited in sportWADA strict-liability framing applies.

    13UK legal position

    UK: Unlicensed (UK)

    Not a licensed medicine. Not approved by the MHRA. Available as a research chemical. Prohibited by WADA and UK Anti-Doping.

    Read the full UK legal guide → Peptides and athletes (UK)

    14EU legal position

    Not authorised by EMA for human use. Classified as an investigational compound. Banned in competitive sports across all EU member states.

    15What this page cannot tell you

    • Whether MK-677 is safe or appropriate for you.
    • What constitutes an acceptable risk-benefit balance in non-deficient adults.
    • What the long-term cardiovascular and glycaemic consequences are at multi-year exposure.
    • Whether the product you might encounter actually contains MK-677.

    16Last reviewed

    Last reviewed:

    Next review due:

    Spotted an error or something out of date? Send a correction.

    17Citation quality score

    BModerate human evidenceQuality of the sources we cite, graded against the evidence grading methodology.

    18Research gaps

    • Phase III development was discontinued by Merck — no completed Phase III data.
    • Long-term safety beyond ~12 months in healthy adults is poorly characterised.
    • Optimal dosing, cycling, and discontinuation strategies not established.

    19Safer alternatives / established care pathways

    • Established weight-training, sleep, and nutrition strategies for body composition.
    • Specialist endocrinology assessment if symptoms suggest genuine GH deficiency.
    • Licensed treatments for documented sarcopenia or frailty per clinical assessment.

    Related Safety Centre page → Athlete anti-doping risks

    20Doctor discussion prompts

    Questions to ask a qualified clinician

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is MK-677 a licensed UK medicine?
    • What are the insulin-resistance and water-retention risks?
    • If I'm an athlete, what is the WADA position?

    Discovery & History

    MK-677 was developed by Merck Research Laboratories in the mid-1990s as part of an effort to create orally active growth hormone secretagogues. The compound emerged from structure-activity relationship studies on non-peptide ghrelin mimetics capable of stimulating GH release via the GHS-R1a receptor. The compound was initially designated L-163,191 before receiving the Merck code MK-677 and the International Nonproprietary Name (INN) ibutamoren. Early pharmacological studies demonstrated that MK-677 could produce dose-dependent increases in GH and IGF-1 when administered orally, which was a significant advancement over injectable peptide alternatives. Phase I and Phase II clinical trials were conducted throughout the late 1990s and 2000s, examining MK-677 in populations including elderly adults, obese individuals, children with GH deficiency, and patients with hip fractures. The compound consistently elevated GH and IGF-1 levels, with secondary benefits observed for body composition, sleep quality, and bone density. However, the HORIZON study in elderly patients with heart failure was terminated early due to a trend toward increased cardiac events, and consistent findings of insulin resistance across multiple trials raised safety concerns. These issues, combined with the availability of recombinant GH therapy, led Merck to discontinue clinical development. Despite never receiving regulatory approval, MK-677 became widely available in the research chemical market and gained popularity due to its oral convenience and potent GH-elevating effects.

    Mechanism of Action

    MK-677 exerts its effects primarily through agonism of the growth hormone secretagogue receptor (GHS-R1a), producing a cascade of endocrine and metabolic effects: **Ghrelin Receptor Agonism** MK-677 binds to and activates GHS-R1a in the pituitary gland and hypothalamus. This triggers GH release from pituitary somatotroph cells through a calcium-dependent signalling pathway distinct from the GHRH receptor pathway. This is the same receptor targeted by endogenous ghrelin. **Sustained GH Elevation** Unlike natural ghrelin (which has a half-life of minutes) or injectable GHRPs (which produce brief GH pulses), MK-677's long plasma half-life (~5 hours, with metabolic effects lasting ~24 hours) produces sustained, non-pulsatile GH elevation. This continuous stimulation pattern differs from the natural pulsatile GH secretion pattern. **IGF-1 Amplification** The sustained GH elevation produced by MK-677 drives hepatic IGF-1 synthesis. Studies consistently show 40-60% increases in serum IGF-1 within 2-4 weeks of daily use, maintained for the duration of administration. IGF-1 mediates many of GH's anabolic effects on muscle, bone, and other tissues. **Appetite Stimulation** As a ghrelin mimetic, MK-677 activates appetite-regulating circuits in the hypothalamus, producing significant increases in hunger and food intake. This is a direct pharmacological effect, not a side effect, and is one of the most consistent findings across all clinical studies. **Cortisol and Prolactin Effects** Some studies report modest, transient increases in cortisol (typically <50% elevation, normalising within weeks) and small increases in prolactin. These effects are generally considered clinically insignificant at standard doses. **Insulin Resistance Mechanism** GH is a counter-regulatory hormone that antagonises insulin action. Sustained GH elevation from MK-677 impairs insulin-mediated glucose disposal, leading to elevated fasting glucose and insulin resistance. This effect has been demonstrated in young, elderly, and obese populations and is the primary safety concern with chronic use.

    Researched Benefits

    Based on preclinical and clinical research findings:

    • 1
      Significant and sustained elevation of GH and IGF-1 levels (40-60% IGF-1 increase) maintained with daily oral dosing
    • 2
      Increased fat-free mass (lean body mass) demonstrated in multiple clinical trials across age groups
    • 3
      Improved sleep quality, particularly Stage IV (deep) sleep duration increased by up to 50% in controlled studies
    • 4
      Enhanced bone mineral density markers with potential for osteoporosis prevention in elderly populations
    • 5
      Oral administration convenience — no injections required, once-daily dosing
    • 6
      Potential for reversing diet-induced nitrogen wasting (anti-catabolic effects in caloric deficit)
    • 7
      Maintained GH/IGF-1 elevation even during caloric restriction, unlike natural GH secretion which often declines
    • 8
      Potential wound healing acceleration through GH/IGF-1 mediated tissue repair pathways

    Claim vs Evidence

    How popular claims about MK-677 stack up against the current research, graded using our public evidence grading methodology.

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Oral GH boost without injections”BYesHighMK-677 does raise GH and IGF-1 levels in human studies; sustained elevation has tolerability concerns (water retention, insulin resistance, appetite increase).
    “Safe long-term for body composition”CLimitedHighInsulin-resistance, water-retention, and congestive-heart-failure concerns are documented; not a UK-licensed long-term agent.
    “Legal because it's not a peptide / not a steroid”ENoHighProhibited at all times under WADA S2 (GH secretagogues). Sale to consumers without authorisation engages UK medicines law.

    Theoretical Dosing & Protocols

    ⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.
    Theoretical Dosage10-25 mg orally per day (most studies used 25 mg; some researchers use 10 mg to reduce side effects)
    FrequencyOnce daily, typically at bedtime to align GH release with natural nocturnal secretion and mitigate daytime hunger
    Duration8-16 weeks in most research contexts; some studies extended to 12-24 months
    NotesThese are theoretical protocols extrapolated from clinical trial dosing. MK-677 is not approved for human use. The 25 mg dose is most studied but carries greater insulin resistance risk. Lower doses (10-12.5 mg) may offer a better risk-benefit profile. Blood glucose, fasting insulin, and IGF-1 should be monitored. Always consult a qualified healthcare professional.

    Administration Routes

    Routes studied in research settings (educational only):

    • Oral administration (primary route — capsule or liquid)
    Half-LifeStability
    Approximately 4-6 hours plasma half-life, but biological effects (IGF-1 elevation) persist for approximately 24 hours due to downstream signallingStable at room temperature in powder or capsule form. Liquid solutions should be stored in a cool, dark place. Does not require refrigeration in solid form.

    Safety Profile & Known Risks

    Commonly Reported Side Effects

    • Significantly increased appetite and food intake (most consistent effect across all studies)
    • Water retention and mild oedema, particularly in the first 2-4 weeks
    • Elevated fasting blood glucose and insulin resistance (dose-dependent, occurs in all populations studied)
    • Lethargy and drowsiness, especially when taken at bedtime
    • Joint stiffness or mild carpal tunnel-like symptoms from fluid retention
    • Transient increase in cortisol levels (usually normalises within 2-4 weeks)
    • Vivid dreams or altered sleep architecture

    Rare Risks & Concerns

    • Development of type 2 diabetes in predisposed individuals (observed in the Nass et al. 12-month study)
    • Potential cardiovascular risk in heart failure patients (HORIZON study terminated early)
    • Modest prolactin elevation (usually clinically insignificant)
    • Theoretical concern regarding IGF-1 and tumour growth promotion in cancer predisposition
    • Potential for pituitary desensitisation with prolonged continuous use

    Contraindications

    • Type 2 diabetes or pre-diabetes (MK-677 worsens insulin resistance)
    • Active cancer or history of cancer (elevated IGF-1 may promote tumour growth)
    • Congestive heart failure or significant cardiovascular disease
    • Pregnancy and breastfeeding (no safety data)
    • Children (except in specific GH deficiency research under medical supervision)
    • Individuals with active pituitary tumours or disorders

    UK & EU Regulatory Context

    🇬🇧 United Kingdom

    Not a licensed medicine. Not approved by the MHRA. Available as a research chemical. Prohibited by WADA and UK Anti-Doping.

    🇪🇺 European Union

    Not authorised by EMA for human use. Classified as an investigational compound. Banned in competitive sports across all EU member states.

    MK-677 has never received regulatory approval from any major authority (FDA, MHRA, EMA). Despite reaching Phase II trials, Merck discontinued development. It is widely available online as a 'research chemical' or 'SARM' (despite not being a SARM). Its sale for human consumption is illegal in most jurisdictions. WADA classifies it as a prohibited substance under S2 (Peptide Hormones, Growth Factors).

    Clinical Studies Summary

    Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults (Nass et al.)

    12-month randomised controlled trial in 65 healthy elderly adults. MK-677 25mg daily increased GH, IGF-1, and fat-free mass (+1.6 kg). However, fasting glucose increased ~7%, HbA1c rose, and 2 participants developed diabetes. Key study establishing both efficacy and the insulin resistance concern.

    Ann Intern Med. 2008View on PubMed

    MK-677 and Sleep Quality (Copinschi et al.)

    In 8 young subjects (aged 18-30) given high-dose (25 mg) MK-677 at bedtime for 7 days, Stage IV (deep) sleep duration increased by approximately 50% and REM sleep by more than 20% versus placebo (p<0.05), with deviations from normal sleep falling from 42% to 8% (p<0.03). A separate cohort of 6 older adults (65-71) given MK-677 for 14 days showed a nearly 50% increase in REM sleep (p<0.05) and reduced REM latency (p<0.02).

    Neuroendocrinology. 1997View on PubMed

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

    Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.

    Neurology. 2008View on PubMed

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

    The proportion of 20K GH in 2-h samples after the initial MK-677 administration was lower than that after 2 and 8 weeks. These moderate changes in the proportion non-22K GH isoforms are likely of small importance for the clinical response to MK-677 treatment.

    Growth Horm IGF Res. 2003View on PubMed

    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.

    In conclusion, the anabolic effect of GH, as produced through the GH secretagogue MK-677, attenuated the indirect suppressive effect of alendronate on bone formation, but did not translate into significant increases in BMD at sites other than the femoral neck.

    J Clin Endocrinol Metab. 2001View on PubMed

    Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).

    At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.

    J Clin Endocrinol Metab. 1999View on PubMed

    Registered Trials & Regulatory Status

    Registered trials
    7
    Currently recruiting
    0
    Furthest phase
    Phase 2
    Approved product
    No

    3 of 5 completed trials have never posted results. Unreported trials are not neutral: results that go unpublished are more often negative ones.

    The Impact of Ibutamoren on Nonalcoholic Fatty Liver Disease

    PHASE2

    Status: Completed · 12 participants · Massachusetts General Hospital

    Conditions: NAFLD, Nonalcoholic Fatty Liver, NASH - Nonalcoholic Steatohepatitis

    Results postedNCT05364684

    Growth Hormone Secretagogue MK-0677's Effect on Lean Body Mass in Chronic Kidney Disease Stage 4/5 Subjects

    PHASE2

    Status: Withdrawn · University of Virginia

    Conditions: Chronic Kidney Disease, Kidney Disease

    No results postedNCT01343641

    Growth Hormone Secretagogue MK-0677 Effect on IGF-1 Levels in ESRD Patients

    NA

    Status: Completed · 49 participants · University of Virginia

    Conditions: Chronic Kidney Disease, End Stage Renal Disease

    Results postedNCT00395291

    Treatment of Sarcopenia in Post-Hip Fracture Patients (0677-032)

    PHASE2

    Status: Terminated · 83 participants · Merck Sharp & Dohme LLC

    Conditions: Hip Fracture

    No results postedNCT00128115

    Efficacy and Safety of an Oral Growth Hormone Drug in the Treatment of Fibromyalgia

    PHASE2

    Status: Completed · 64 participants · Bennett, Robert, M.D.

    Conditions: Fibromyalgia

    No results postedNCT00116129

    Study of MK0677 for the Treatment of Alzheimer's Disease (0677-030)(COMPLETED)

    PHASE2

    Status: Completed · 512 participants · Merck Sharp & Dohme LLC

    Conditions: Alzheimer's Disease

    No results postedNCT00074529

    Effects of an Oral GH Secretagogue (MK-677) on Body Composition and Functional Ability of Older Adults

    PHASE1/PHASE2

    Status: Completed · 72 participants · University of Virginia

    Conditions: Aging

    No results postedNCT00474279

    Adverse event reports (FDA FAERS)

    Not applicable: no licensed product contains this peptide, so it is not reported through FAERS. This is an absence of surveillance, not evidence of safety.

    Source: ClinicalTrials.gov and openFDA. Updated automatically.

    Looking for MK-677?

    Source research-grade MK-677 from a trusted UK supplier — third-party tested with certificate of analysis.

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    Frequently Asked Questions

    Questions to ask a qualified clinician about MK-677

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is MK-677 a licensed UK medicine?
    • What are the insulin-resistance and water-retention risks?
    • If I'm an athlete, what is the WADA position?

    UK regulatory & safety context

    Peptides and athletes (UK)

    UK legal reference

    Athlete anti-doping risks

    Safety Centre guide

    Related Research Guides

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    MK-677 vs CJC-1295 + Ipamorelin

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