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MK677 supplement bottle labeled 10 mg, Batch No.004, dated 23-07-2025, with two white capsules, shown on a beige background. Pharmaceutical packaging for MK-677 Ibutamoren peptide in capsule form
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MK677(Ibutamoren) 100x10mg

MK677(Ibutamoren) 100x10mg

€65,00 EUR
Taxes included.

NOT FOR HUMAN CONSUMPTION

MK677 (ibutamoren) is an oral, non-peptide ghrelin-receptor (GHSR-1a) agonist that provokes pulsatile growth-hormone (GH) release and raises circulating IGF-1. Unlike injectable secretagogues (GHRP-2/hexarelin), MK-677 is once-daily oral, engages central orexigenic circuits (NPY/AgRP), and modestly elevates cortisol and prolactin. It does not activate the androgen receptor and is not a SARM. MK-677 is not FDA/EMA-approved and is prohibited by WADA as a GH-releasing substance.

Additional Benefits of MK-677 Now Under Investigation

Benefit Key take-aways
1 Lean-mass accrual in older adults Daily MK-677 increases fat-free mass over months with parallel IGF-1 rises, approximating youthful GH/IGF-1 levels; strength/function show supportive trends when combined with resistance training. <br/><em>Annals of Internal Medicine; JCEM</em>
2 Bone-turnover & BMD signals Increases bone-formation markers (e.g., P1NP, osteocalcin) and reduces resorption markers; longer-term cohorts report BMD improvements, supporting anti-frailty potential. <br/><em>Bone; Osteoporosis International</em>
3 Sleep architecture Slow-wave sleep (SWS) and REM density improve with bedtime dosing, aligning with physiologic GH pulses and next-day vitality. <br/><em>Sleep; Psychoneuroendocrinology</em>
4 Appetite & weight in catabolic states Robust orexigenic effect increases caloric intake; cachexia/rehab pilots show weight and FFM gainswith acceptable tolerability. <br/><em>Clinical Nutrition; Supportive Care in Cancer</em>
5 Glucose handling (mixed) Some studies show insulin-sensitivity drift (↑ fasting glucose/insulin); others report neutral outcomes with lifestyle control—underscores need for glycaemic monitoring. <br/><em>Diabetes Care; Metabolism</em>
6 Functional recovery after illness/injury Early programs evaluate MK-677 to speed rehabilitation, leveraging appetite + anabolic endocrine support. <br/><em>Geriatrics & Gerontology International; Archives of Physical Medicine & Rehabilitation</em>
7 GH-axis restoration in age-related decline Elevates IGF-1/IGFBP-3 toward youthful ranges without exogenous GH injections; preserves pulsatility. <br/><em>Endocrine Reviews; JCEM</em>
8 Quality-of-life domains Participants frequently report better sleep quality, appetite, and recovery; validated PROs are being incorporated into trials. <br/><em>Endocrine Practice; Quality of Life Research</em>
9 Convenience & adherence Once-daily oral regimen improves persistence versus injectable GH or peptide secretagogues. <br/><em>Clinical Therapeutics; Patient Preference and Adherence</em>

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

MK-677 binds GHSR-1a (GPCR) on hypothalamic neurons and pituitary somatotrophs → Gαq/11–PLC–IP₃/Ca²⁺signaling → GH vesicle exocytosis. It synergizes with endogenous GHRH and is partly countered by somatostatin. Central GHSR activation also drives NPY/AgRP orexigenic pathways and modulates sleep circuits.

2.2 Down-stream Biology

Pathway Functional outcome Context
GH → GHR–JAK2–STAT5 ↑ IGF-1/IGFBP-3, ↑ protein synthesis, lipolysis Liver, muscle, adipose
GHSR → NPY/AgRP ↑ appetite, ↑ gastric motility Hypothalamus/GI
Sleep–GH coupling ↑ SWS/REM consolidation, nocturnal GH pulses CNS
Bone turnover signals ↑ formation markers; BMD over time Skeleton

3. Pharmacokinetics

  • Route: Oral (once daily).

  • Absorption: Rapid; Tmax ~1–2 h.

  • Half-life: ~4–6 h; IGF-1 elevation persists 24 h with daily dosing due to GH-axis dynamics.

  • Metabolism: Hepatic; CYP3A4 involvement reported in vitro (DDI potential with strong inhibitors/inducers).

  • Elimination: Hepatic/renal metabolites; high protein binding.

4. Pre-clinical and Translational Evidence

4.1 Aging/Sarcopenia

Randomized trials in older adults show sustained IGF-1 increases, FFM gains, improved sleep architecture, and favorable trends in strength and gait measures, particularly with structured exercise.

4.2 Bone Health

Markers of bone formation rise within weeks; BMD benefits emerge over longer courses—supporting evaluation for osteopenia/osteoporosis in frailty.

4.3 Metabolism & Diabetes Risk

In mixed-risk cohorts, MK-677 may raise fasting glucose/insulin and reduce insulin sensitivity; effects are dose-, duration-, and phenotype-dependent, emphasizing glycaemic monitoring.

Evidence quality note: Human data include multiple small–moderate RCTs and mechanistic studies; long-term outcomes (fractures, disability, CV events) remain unresolved.

5. Emerging Clinical Interests

Field Rationale Current status
Sarcopenia/frailty Oral anabolic + sleep and appetite support Phase 2–style signals; larger RCTs needed
Osteopenia/osteoporosis Bone-turnover and BMD improvements Exploratory
Cachexia (cancer/COPD/CHF) Orexigenic + GH/IGF-1 anabolism Pilot/feasibility
Post-acute rehab Appetite/FFM restoration to aid recovery Early translational
Sleep disorders (SWS decline) SWS augmentation with endocrine coupling Proof-of-concept

6. Safety and Tolerability

  • Common: Increased appetite/weight, peripheral edema, transient paresthesias/carpal-tunnel-like symptoms, fatigue, vivid dreams.

  • Endocrine: IGF-1 elevation (target age-normal range); prolactin and cortisol may rise modestly.

  • Metabolic: FPG/HbA1c can drift upward; monitor in prediabetes/diabetes and adjust therapy as needed.

  • CV/Renal: Edema and mild BP increases can occur—use caution in HF/CKD.

  • GI: Nausea/GERD in a minority.

  • Neuropsych: Rare insomnia/irritability.

  • Drug interactions: Caution with strong CYP3A4 inhibitors/inducers (theoretical/limited clinical data).

  • Contraindications/Caution: Active malignancy under evaluation (IGF-1 biology), pregnancy, uncontrolled diabetes, decompensated HF.

Comparative safety matrix

Concern MK-677 (oral GHSR agonist) GHRP-2/Hexarelin (injectable) Sermorelin/CJC (GHRH analogs) Somatropin (GH)
Route/frequency Oral, once daily SC/IN multiple daily SC nightly / weekly-biweekly (DAC) SC/IM daily–weekly
IGF-1 profile Sustained, higher Pulsatile, moderate Physiologic pulses Dose-driven, sustained
Appetite ↑↑ (orexigenic) ↑ (variable) Neutral Neutral
Edema/CTS Moderate Mild–moderate Low–moderate Moderate
Glycaemic drift Common (mild–mod.) Mild Neutral–mild ↑ Neutral–mild ↑
Prolactin/cortisol Modest ↑ Transient ↑ Minimal Minimal

7. Regulatory Landscape

  • Approvals: None for any indication in major markets.

  • Sport: WADA-prohibited (S2: growth-hormone releasing substances).

  • Supply: Often sold as a research chemical; purity/adulteration issues are common outside GMP trials.

8. Future Directions

  • Large, outcome-focused RCTs in sarcopenia/frailty with function and fall/fracture endpoints.

  • Bone programs powered for BMD and fracture outcomes.

  • Metabolic risk management (pre-specified glycaemic thresholds, CGM, cardiometabolic composites).

  • Dosing/time-of-day studies to optimize sleep/SWS and minimize glycaemic drift.

  • Combination strategies: Pair with resistance exercise, protein optimization, or incretin-based therapies to balance orexigeny with metabolic safety.

  • DDI characterization for CYP3A4 interactions and special-population PK.

Selected References

  • Annals of Internal Medicine; Journal of Clinical Endocrinology & Metabolism — MK-677 increases IGF-1 and fat-free mass in older adults.

  • Sleep; Psychoneuroendocrinology — Improvements in slow-wave sleep and nocturnal GH coupling.

  • Bone; Osteoporosis International — Bone-turnover markers and BMD trends under ghrelin mimetics.

  • Diabetes Care; Metabolism — Glycaemic effects and insulin-sensitivity considerations.

  • Clinical Pharmacology & Therapeutics — Oral PK/PD characteristics of ghrelin-receptor agonists.

  • Supportive Care in Cancer; Clinical Nutrition — Appetite/weight and functional recovery in catabolic states.

  • Endocrine Reviews — Physiology of GH pulsatility and ghrelin signaling.

  • Drug Testing & Analysis; WADA Prohibited List — Anti-doping status and detection.