MK-677 (Ibutamoren)
Growth Hormone / IGF-1 AxisPhase 2Also known as: Ibutamoren
MK-677 (also called Ibutamoren or Nutrobal) is an orally-active, non-peptide ghrelin receptor (GHS-R1a) agonist developed by Merck Research Laboratories in the 1990s. Unlike Ipamorelin, GHRP-2, or hexarelin — all of which are peptides requiring subcutaneous injection — MK-677 is a small-molecule drug with high oral bioavailability, making it the only clinically-studied oral growth hormone secretagogue. MK-677 activates the same GHS-R1a receptor as endogenous ghrelin and produces a strong, sustained GH and IGF-1 elevation with a single daily oral dose.
Overview
At A Glance
MK-677 is a small-molecule full agonist at the growth hormone secretagogue receptor 1a (GHS-R1a) — the same receptor activated by endogenous ghrelin and the peptide GHS compounds (Ipamorelin, GHRP-2, GHRP-6, hexarelin). What distinguishes MK-677 is its pharmacokinetics and chemis…
Mechanism of Action
MK-677 is a small-molecule full agonist at the growth hormone secretagogue receptor 1a (GHS-R1a) — the same receptor activated by endogenous ghrelin and the peptide GHS compounds (Ipamorelin, GHRP-2, GHRP-6, hexarelin). What distinguishes MK-677 is its pharmacokinetics and chemistry, not its primary receptor biology.
1. GHS-R1a agonism (Gq/11 / PLC / IP3 / Ca2+ pathway)
- GHS-R1a is a Class A GPCR expressed on pituitary somatotrophs (primary target for GH release) and at lower density on hypothalamic arcuate nucleus, gastric cells, pancreatic islets, and cardiomyocytes
- Ligand binding activates Gq/11, triggering phospholipase-C, which cleaves PIP₂ into IP₃ and DAG
- IP₃ mobilizes intracellular Ca²⁺; DAG activates PKC
- Net effect: depolarization of the somatotroph and rapid exocytosis of preformed GH granules
MK-677 has an in vivo EC₅₀ of approximately 1-3 nM at GHS-R1a — comparable to native ghrelin and the peptide GHS agonists (Murphy et al., 1998).
2. The critical difference: 24-hour half-life and sustained receptor engagement
This is where MK-677 diverges from all other GHS peptides:
| Compound | Half-life | Dosing | GH Profile |
|---|---|---|---|
| Ipamorelin | ~2 hours | 1-3x daily SC | Discrete pulses |
| GHRP-2 / GHRP-6 | ~20-30 min | 2-3x daily SC | Discrete pulses |
| MOD-GRF 1-29 | ~30 min | 1-3x daily SC | Discrete pulses (GHRH pathway) |
| Tesamorelin | ~30-50 min | 1x daily SC | Daily pulse |
| MK-677 | ~24 hours | 1x daily oral | Sustained amplification |
MK-677's 24-hour half-life produces sustained amplification of all GH pulses throughout the day rather than one or two discrete superimposed pulses. This is a double-edged property:
- Positive: Consistent IGF-1 elevation, once-daily oral convenience, stronger cumulative body composition effects
- Negative: Greater water retention, more appetite stimulation, more insulin resistance, and theoretical concerns about somatotroph desensitization with prolonged use
3. Pulsatility — preserved but dampened
Despite sustained receptor engagement, MK-677 does not fully abolish the pulsatile GH architecture. Somatostatin-mediated negative feedback can still modulate GH between pulses, and 24-hour GH profiling shows MK-677 increases both pulse amplitude and mean GH concentration without fully flattening the rhythm (Copinschi et al., 1997). This is a more favorable profile than CJC-1295-DAC's continuous GH elevation but less physiologic than ipamorelin's discrete pulses.
4. Downstream IGF-1 elevation
MK-677 produces the strongest sustained IGF-1 elevation of any oral or injectable GHS in non-GH-deficient adults:
- Week 2-4: IGF-1 rises ~50% from baseline
- Steady state at 4-8 weeks: IGF-1 ~80-100% elevated
- In the Nass 2008 2-year trial, mean IGF-1 rose from 180 to 283 ng/mL on MK-677 25 mg/day
5. Ghrelin-receptor effects beyond GH release
Because GHS-R1a is expressed widely, MK-677's sustained 24-hour agonism produces more prominent non-GH effects than the peptide GHS compounds:
- Appetite stimulation — the most noticeable secondary effect; direct action on hypothalamic NPY/AgRP neurons; can increase caloric intake by 20-30% if not actively controlled
- Gastric emptying — accelerated; may cause mild GI discomfort in some users
- Insulin resistance — multi-mechanism: GH-mediated hepatic glucose output increase, ghrelin-mediated glucose intolerance, fluid-shift-related changes; meaningfully worse on MK-677 than ipamorelin at equivalent GH exposure
- Slow-wave sleep enhancement — consistent with GHS pharmacology; often reported as the most immediately noticeable benefit
- Cortisol and prolactin — MK-677 is generally selective like ipamorelin, producing minimal elevations at clinical doses (much less than GHRP-2/6); however at high doses (>50 mg/day) some cortisol elevation has been reported
Overview
MK-677 (also called Ibutamoren or Nutrobal) is an orally-active, non-peptide ghrelin receptor (GHS-R1a) agonist developed by Merck Research Laboratories in the 1990s. Unlike Ipamorelin, GHRP-2, or hexarelin — all of which are peptides requiring subcutaneous injection — MK-677 is a small-molecule drug with high oral bioavailability, making it the only clinically-studied oral growth hormone secretagogue.
MK-677 activates the same GHS-R1a receptor as endogenous ghrelin and produces a strong, sustained GH and IGF-1 elevation with a single daily oral dose. In the key 2-year trial in older adults, MK-677 25 mg/day elevated mean IGF-1 from ~180 ng/mL to ~280 ng/mL and produced measurable increases in lean body mass (Nass et al., 2008).
The defining pharmacokinetic feature is the ~24-hour plasma half-life, which enables once-daily dosing and produces a sustained elevation of GH pulse amplitude throughout the day rather than the discrete 2-3 hour pulse of injectable GHS peptides. This is mechanistically distinct from the pulsatile GH architecture preserved by Ipamorelin, Tesamorelin, and MOD-GRF 1-29 — and is the source of both MK-677's popularity (convenience, durable IGF-1 elevation) and its characteristic side-effect profile (greater water retention, appetite stimulation, and insulin resistance than the injectable GHS peptides).
MK-677 reached Phase 3 trials for pediatric growth hormone deficiency, geriatric sarcopenia, and hip fracture recovery. Despite positive efficacy signals, Merck discontinued development in the early 2010s, and the compound is not FDA-approved for any indication. It remains widely available as a research-use oral supplement and is one of the most popular compounds in the biohacking and bodybuilding communities specifically because of its oral route, 24-hour half-life, and significant effects on body composition, sleep, and appetite.
Typical dosing: 10-25 mg orally, once daily (typically pre-bed). Doses above 25 mg provide minimal additional benefit and increase side effects proportionally.
Regulatory status: Not FDA-approved. Sold as a research chemical in the US; WADA-banned for competitive athletes. Commonly used off-label in integrative medicine and is heavily represented in biohacking protocols. See our MK-677 Dosage Guide for protocol specifics and our Ipamorelin vs MK-677 comparison for stack-selection context.
Potential Research Fields
Chemical Information
IUPAC Name
2-amino-2-methyl-N-[1-(methylsulfonylmethyl)-2-(1-methylpropyl)-3-(1H-indol-3-ylmethyl)...] (complex structure)
CAS Number
159634-47-6
Molecular Formula
C27H36N4O5S
Molecular Mass
528.67 g/mol
Dosing & Protocols
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Research
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Interactions
Interaction Matrix
Contraindications
Absolute contraindications
- History of congestive heart failure (CHF) or any NYHA class II-IV cardiac dysfunction — the Nass 2008 trial reported 3/32 active-arm patients developing transient CHF symptoms; MK-677's water retention and sustained GH elevation can precipitate decompensation in vulnerable hearts
- Active malignancy — GH/IGF-1 axis may accelerate tumor growth. No direct MK-677 cancer data but inferred from general GH/IGF-1 literature (Renehan et al., 2004)
- Active diabetic retinopathy (proliferative or severe non-proliferative) — GH elevation can worsen retinopathy
- History of acromegaly or pituitary adenoma — superimposing sustained exogenous GH amplification on an already-hyperactive axis risks accelerating tumor growth and acromegalic progression
- Pregnancy or breastfeeding — no safety data; do not use
- Age <18 — pediatric GHD is managed with sermorelin or recombinant GH under endocrinology supervision, not MK-677
Relative contraindications (consult physician before use)
- Type 2 diabetes or pre-diabetes — MK-677 produces measurable glucose intolerance; use requires close monitoring and usually metformin co-therapy
- Uncontrolled hypertension — fluid retention can exacerbate blood pressure
- History of carpal tunnel syndrome — fluid retention and connective tissue expansion can worsen symptoms
- Hypothyroidism — optimize thyroid first
- Chronic kidney disease (CKD stage III+) — fluid retention can contribute to edema; dose reduction and close monitoring
- History of pituitary or hypothalamic surgery or radiation — altered somatotroph response; unpredictable
Drug interactions
- Insulin and oral hypoglycemics — MK-677 impairs glucose tolerance; antidiabetic medication may need adjustment
- Corticosteroids (chronic systemic) — suppress GH axis and blunt MK-677 response
- CYP3A4 inhibitors/inducers — MK-677 is CYP3A4 metabolized; major inhibitors (ketoconazole, ritonavir) can elevate plasma levels; inducers (rifampin, carbamazepine) can reduce efficacy
- Exogenous GH (Somatropin) — do not combine
- Other GHS peptides or CJC-1295-DAC — do not combine (redundant, additive side effects)
Specific drug combinations that require caution
- SSRI + MK-677 — no direct interaction but both can cause fluid retention; monitor
- NSAID chronic + MK-677 — both retain fluid; monitor edema
- Statins + MK-677 — no specific interaction; standard monitoring
Monitoring requirements
- Baseline: IGF-1, fasting glucose, HbA1c, insulin, complete metabolic panel, thyroid panel, CBC, lipid panel, PSA (men >40), echocardiogram if any cardiac history
- Week 4-6: IGF-1, fasting glucose, insulin
- Week 8-12: Full panel + blood pressure + weight trend
- Every 12 weeks on long-term therapy: Full panel
- Annually: Full panel + consider imaging if symptomatic
Discontinuation criteria
Stop MK-677 and consult a clinician if you develop:
- Any chest pain, dyspnea, peripheral edema with weight gain >3 kg, orthopnea — possible CHF; urgent
- New or worsening carpal tunnel symptoms
- IGF-1 > 350 ng/mL (supraphysiologic in most adults)
- Fasting glucose consistently >115 mg/dL or HbA1c rising >0.4 points despite metformin
- Any new palpable mass, changing mole, unexplained weight loss (cancer workup)
- Severe headache, visual changes (rule out pituitary pathology)
- Unexplained fatigue, edema, or rapid weight gain (assess fluid balance, thyroid, glucose)
Research Disclaimer
This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.
$74.99
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| Vendor | Product | Form | Qty | Price | $/mg | Coupon | |
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MK-677 Capsules 60ct | capsule | 60 capsules● In Stock | $74.99BEST | — |
Tracking since Apr 6, 2026 · 1 data point
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Related Compounds
View AllCJC-1295 (Mod GRF 1-29)
Growth Hormone / IGF-1 AxisPreclinicalCJC-1295 without DAC (also called Modified GRF 1-29 or MOD-GRF 1-29) is a 30-amino-acid analog of the first 29 residues of endogenous Growth Hormone Releasing Hormone (GHRH), with four strategic substitutions (D-Ala² for DPP-4 resistance, Gln⁸, Ala¹⁵, Leu²⁷) that extend its plasma half-life from <2 minutes (native GHRH) to ~30 minutes.
CJC-1295 with DAC
Growth Hormone / IGF-1 AxisPhase 2CJC-1295 with DAC (Drug Affinity Complex) is a modified form of CJC-1295 that incorporates a maleimidopropionic acid (MPA) reactive group at the C-terminus.
GHRP-2
Growth Hormone / IGF-1 AxisPhase 2GHRP-2 (growth hormone-releasing peptide-2), also known as pralmorelin and KP-102, is a synthetic hexapeptide growth hormone secretagogue that was among the first GHRPs developed in the seminal research of Cyril Bowers and colleagues at Tulane University in the late 1980s and early 1990s.
GHRP-6
Growth Hormone / IGF-1 AxisPhase 2GHRP-6 (growth hormone-releasing peptide-6) is a synthetic hexapeptide with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 that binds the ghrelin receptor (GHS-R1a) to stimulate endogenous growth hormone release.
Hexarelin
Growth Hormone / IGF-1 AxisPhase 2Hexarelin (also called examorelin) is a potent synthetic hexapeptide growth hormone secretagogue with the sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2.
IGF-1 LR3
Growth Hormone / IGF-1 AxisPhase 2IGF-1 LR3 (Long R3 IGF-1) is a synthetic analog of human insulin-like growth factor 1 modified at two positions to dramatically extend its serum half-life and amplify its tissue bioactivity compared to native IGF-1.
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Protocols, calculator & safety for MK-677 (Ibutamoren)
Research Score
46 PubMed studies
Quality Indicators
Data Completeness
100%Research Credibility
Quick Facts
Half-Life
~24 hours (oral)
Molecular Weight
528.67 g/mol
Administration
oral
CAS Number
159634-47-6
Trial Phase
Phase 2
Safety Profile
Moderate RiskCommon Side Effects
- • Increased appetite
- • Water retention
- • Lethargy
- • Elevated fasting glucose
- • Increased cortisol
Stop Use If
- Active cancer
- Uncontrolled diabetes or insulin resistance
- Active edema
Research Disclaimer
This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use.
Frequently Asked Questions
Is MK-677 a SARM or a steroid?
Neither. MK-677 (Ibutamoren) is a growth hormone secretagogue — a small-molecule agonist at the ghrelin receptor (GHS-R1a) that stimulates the pituitary to release more growth hormone. It has no direct androgen receptor activity (unlike SARMs) and is not a steroid. The receptor it activates is the same one activated by the natural hunger hormone ghrelin. MK-677 increases your body's own GH and IGF-1 production via the pituitary; it does not introduce exogenous hormones. This mechanistic distinction matters for side-effect profile and regulatory classification.
How much IGF-1 will MK-677 raise my levels by?
At the standard 25 mg/day dose, IGF-1 typically rises 80-100% above baseline and reaches steady state within 4-8 weeks. In the pivotal Nass 2008 2-year trial in older adults, mean IGF-1 rose from 180 to 283 ng/mL (57% in that older population; younger healthy adults typically see larger percentage increases). At the lower 10 mg/day dose, expect ~40-50% IGF-1 elevation. Above 25 mg/day the dose-response plateaus — higher doses do not produce proportional IGF-1 elevation but do produce proportional side effects.
Why does MK-677 cause so much water retention and hunger compared to ipamorelin?
The 24-hour half-life of MK-677. Ipamorelin clears in ~2 hours, producing a discrete 2-3 hour GH pulse and transient appetite effect. MK-677 remains active at the ghrelin receptor around the clock, producing sustained GH elevation AND continuous ghrelin-receptor tone. The continuous ghrelin signal drives the hunger effect directly (ghrelin is the hunger hormone), and the sustained GH elevation drives fluid shifts and water retention. This is also why MK-677 causes more insulin resistance than injectable GHS peptides at equivalent total GH exposure — sustained vs pulsatile receptor engagement produces different downstream metabolic effects.
Does MK-677 shut down natural GH production?
The evidence is nuanced. In the Nass 2008 2-year trial, GH and IGF-1 remained elevated throughout the study — no evidence of tachyphylaxis. Some users report reduced subjective response after 3-4 months of continuous use, but this has not been consistently demonstrated in controlled trials. Because MK-677 preserves some pulsatility (unlike CJC-1295 with DAC), somatostatin-mediated negative feedback can still operate between pulses — which reduces (but does not eliminate) long-term desensitization risk. The conservative approach is cycling 8-16 weeks on / 4-6 weeks off; the Nass-trial-reference approach is continuous dosing with quarterly bloodwork.
What's the difference between MK-677 and injectable growth hormone secretagogues like ipamorelin?
Four key differences: (1) Route — MK-677 is oral, ipamorelin is subcutaneous injection; (2) Pharmacokinetics — MK-677 has a 24-hour half-life producing sustained amplification, ipamorelin has a 2-hour half-life producing discrete pulses; (3) Side effects — MK-677 produces more water retention, appetite stimulation, and glucose intolerance due to sustained receptor engagement; ipamorelin is cleaner but less convenient; (4) Stacking — ipamorelin pairs with GHRH analogs for 3-5x pulse amplification; MK-677 is used standalone because its sustained signal already amplifies endogenous GHRH pulses. Both target the same receptor (GHS-R1a).
Should I take MK-677 with food or on an empty stomach?
Empty stomach preferred. Fasted dosing produces approximately 15% higher Cmax than fed dosing. Pre-bed (2+ hours after last meal) is standard: (1) maximizes absorption, (2) aligns with the nocturnal GH burst, (3) enhances slow-wave sleep. If empty stomach is not practical, MK-677 can be taken with food — the efficacy penalty is small (~15%). Avoid high-fat meals immediately before dosing as they more meaningfully slow absorption. Alcohol does not significantly interact pharmacologically but impairs sleep quality — avoid within 4 hours of dosing for full sleep-architecture benefit.
Is MK-677 safe for long-term use?
The best data we have is the Nass 2008 trial (2 years in older adults, 25 mg/day), which showed sustained IGF-1 elevation and lean mass gain with modest HbA1c rise (~0.1%) and 3/32 patients developing transient CHF symptoms. Beyond 2 years, safety is extrapolated from general GH/IGF-1 literature. The safety considerations are: (1) glucose intolerance is real and dose-dependent — manage with diet, monitoring, and metformin if needed; (2) fluid retention should be monitored, especially in users with any cardiac history (absolute contraindication if CHF); (3) IGF-1 elevation should stay within age-adjusted reference range — periodic monitoring is required. For most healthy users, 12-16 weeks on / 4-6 weeks off with full bloodwork is the conservative approach; continuous use is defensible with monitoring but not fully characterized beyond 2 years.
Can I stack MK-677 with semaglutide or TRT?
Yes to both. MK-677 + semaglutide or tirzepatide is a body recomposition stack: GLP-1 drives caloric deficit and fat loss, MK-677 preserves lean body mass via GH/IGF-1 elevation. The appetite dimensions run in opposite directions — GLP-1 suppresses, MK-677 stimulates — net is usually still hypocaloric but less aggressively so. For more moderate appetite balance, use MK-677 at 10 mg instead of 25 mg. MK-677 + TRT is complementary: HPG and GH axes are independent and combined optimization is standard in integrative hormone clinics. Add metformin 500-1000 mg/day if glucose management is a concern. DO NOT stack MK-677 with ipamorelin, GHRP-2/6, or hexarelin — all are GHS-R1a agonists, making the combination redundant.
Is MK-677 legal and is it banned in sports?
MK-677 is not FDA-approved for any indication. It is sold as a research chemical in the United States — legal to possess, research, and sell with appropriate labeling; enforcement on personal use varies. Some integrative medicine clinics prescribe it off-label through compounding pharmacies. WADA (World Anti-Doping Agency) has banned MK-677 in competitive athletics since 2012 — it is on the S2 prohibited list (peptide hormones, growth factors, related substances). If you are a competitive athlete subject to testing, MK-677 will produce a positive result for up to 6 weeks after discontinuation. See our Best Peptide Vendors 2026 guide for sources; always verify HPLC purity and COA before use.
How long does it take to see results from MK-677?
Timeline from Phase 3 data: (1) Sleep quality improvement — most users report deeper sleep within 3-7 nights; this is the most immediate noticeable effect; (2) Appetite increase — immediate (days 1-3); (3) Water retention / scale weight increase — 1-3 kg in the first 2 weeks; stabilizes by week 4; (4) IGF-1 rise — detectable at week 2, reaches steady state at 4-8 weeks; (5) Lean body mass gain — measurable at 8-12 weeks, continues to accrue over months (Nass 2008 showed 1.1 kg gain at 24 months); (6) Subjective recovery improvement — most users report this at weeks 2-4; (7) Body composition change — fat loss is modest unless caloric deficit maintained; lean mass gain is the primary visible effect. Discontinuation reverses effects over 2-4 weeks.
Research Tools
Related Compounds
View AllCJC-1295 (Mod GRF 1-29)
Growth Hormone / IGF-1 AxisPreclinicalCJC-1295 without DAC (also called Modified GRF 1-29 or MOD-GRF 1-29) is a 30-amino-acid analog of the first 29 residues of endogenous Growth Hormone Releasing Hormone (GHRH), with four strategic substitutions (D-Ala² for DPP-4 resistance, Gln⁸, Ala¹⁵, Leu²⁷) that extend its plasma half-life from <2 minutes (native GHRH) to ~30 minutes.
CJC-1295 with DAC
Growth Hormone / IGF-1 AxisPhase 2CJC-1295 with DAC (Drug Affinity Complex) is a modified form of CJC-1295 that incorporates a maleimidopropionic acid (MPA) reactive group at the C-terminus.
GHRP-2
Growth Hormone / IGF-1 AxisPhase 2GHRP-2 (growth hormone-releasing peptide-2), also known as pralmorelin and KP-102, is a synthetic hexapeptide growth hormone secretagogue that was among the first GHRPs developed in the seminal research of Cyril Bowers and colleagues at Tulane University in the late 1980s and early 1990s.
GHRP-6
Growth Hormone / IGF-1 AxisPhase 2GHRP-6 (growth hormone-releasing peptide-6) is a synthetic hexapeptide with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 that binds the ghrelin receptor (GHS-R1a) to stimulate endogenous growth hormone release.
Hexarelin
Growth Hormone / IGF-1 AxisPhase 2Hexarelin (also called examorelin) is a potent synthetic hexapeptide growth hormone secretagogue with the sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2.
IGF-1 LR3
Growth Hormone / IGF-1 AxisPhase 2IGF-1 LR3 (Long R3 IGF-1) is a synthetic analog of human insulin-like growth factor 1 modified at two positions to dramatically extend its serum half-life and amplify its tissue bioactivity compared to native IGF-1.
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