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The Peptide Effect
phase 2Growth Hormone

MK-677

Also known as: Ibutamoren, Ibutamoren Mesylate, MK-0677, L-163,191, Oratrope

MK-677 (ibutamoren) is a non-peptide, orally active growth hormone secretagogue that mimics ghrelin by binding to the GHS-R1a receptor. Although technically a small molecule rather than a peptide, it is commonly grouped with GH secretagogue peptides due to its identical mechanism of action. Its oral bioavailability and long half-life (~24 hours) make it the most convenient GH secretagogue available, requiring only once-daily dosing without injections. MK-677 has been studied in clinical trials for muscle wasting, osteoporosis, and GH deficiency.

Key Facts

Mechanism
MK-677 is a non-peptide spiropiperidine compound that acts as a potent, long-acting agonist of the growth hormone secretagogue receptor (GHS-R1a) — the endogenous receptor for ghrelin. It mimics ghrelin's effects on the pituitary, hypothalamus, and other tissues. Upon binding GHS-R1a, MK-677 stimulates pulsatile GH release from somatotroph cells, increases circulating IGF-1 levels, and activates appetite-regulating pathways in the hypothalamus. Its non-peptide structure confers oral bioavailability and resistance to enzymatic degradation, resulting in a sustained 24-hour duration of action that maintains elevated GH pulsatility throughout the day and night.
Research Status
phase 2
Half-Life
~24 hours
Molecular Formula
C₂₇H₃₆N₄O₅S
Primary Use
Growth Hormone
Table of Contents

Benefits

  • Sustained GH and IGF-1 elevation with once-daily oral dosing — no injections neededstrong
  • Convenient oral administration — one of very few effective oral GH secretagoguesstrong
  • Significantly improved sleep quality, especially increased REM and stage 4 slow-wave sleepmoderate
  • Improved bone mineral density in elderly populations with long-term usemoderate
  • Preservation of lean body mass, particularly relevant in catabolic states and agingmoderate
  • Improved nitrogen balance and may counteract protein catabolism during caloric restrictionmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Oral10–25 mgOnce daily, typically at bedtimeBedtime dosing leverages the natural nocturnal GH surge and allows users to sleep through the hunger spike. Start at 10 mg to assess tolerance.
Oral12.5 mgOnce dailyConservative dose balancing GH/IGF-1 elevation with reduced side effects; commonly used for anti-aging and general health optimization
Oral25 mgOnce dailyMaximum commonly used dose. Higher doses may increase insulin resistance without proportional GH benefit. Monitor fasting glucose and HbA1c.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Increased appetite and hunger (potent ghrelin receptor activation)common
  • Water retention, bloating, and puffiness (especially facial)common
  • Insulin resistance and elevated fasting blood glucose with chronic useserious
  • Numbness and tingling in hands (paresthesia)common
  • Lethargy and fatigue, particularly at higher dosescommon
  • Joint pain from fluid retention or GH/IGF-1 elevationrare

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Frequently Asked Questions

How does MK-677 compare to injectable HGH?
MK-677 stimulates your body's own GH production through the ghrelin receptor, while HGH injections deliver exogenous growth hormone directly. MK-677 is oral, convenient, and significantly cheaper ($30–100/month vs $500–2,000+/month for HGH). However, HGH produces much higher, more controllable GH levels and does not cause the appetite or insulin resistance issues associated with ghrelin receptor activation. MK-677 is a practical alternative for those seeking moderate GH elevation without injections, but cannot replicate the GH levels achievable with pharmaceutical HGH.
Does MK-677 cause insulin resistance?
Yes. MK-677 can increase fasting blood glucose and reduce insulin sensitivity, particularly with chronic use at higher doses (25 mg). This is partly due to the anti-insulin effects of sustained GH elevation and partly due to direct ghrelin pathway activation. In clinical trials, fasting glucose increased by approximately 5–10 mg/dL on average. Individuals with pre-existing insulin resistance, metabolic syndrome, or type 2 diabetes should use extreme caution. Regular monitoring of fasting glucose and HbA1c is strongly recommended. Some users mitigate this with berberine, metformin, or dietary carbohydrate management.
Is MK-677 a SARM?
No. MK-677 is not a SARM (Selective Androgen Receptor Modulator). It does not interact with androgen receptors and has no direct effect on testosterone, estrogen, or other sex hormones. It is a growth hormone secretagogue that works through the ghrelin receptor. MK-677 is often sold alongside SARMs by research chemical vendors, which causes this common misconception. It does not require post-cycle therapy (PCT) as it does not suppress the HPTA axis.
What is the legal status of MK-677?
MK-677 exists in a regulatory gray area in most countries. In the United States, it is not FDA-approved for any medical use and is not a scheduled controlled substance. It is sold as a "research chemical" and is widely available online. WADA (World Anti-Doping Agency) has banned it in competitive sports. The FDA has issued warning letters to companies marketing it for human consumption. Legal status varies internationally — some countries classify it as a prescription medicine or prohibit its sale entirely. This is not legal advice.
Is MK-677 safe for long-term use?
MK-677 has been studied in clinical trials lasting up to 2 years (in elderly populations), with the primary safety concerns being insulin resistance, increased appetite, and fluid retention. No serious adverse events attributable to MK-677 were identified in these studies. However, long-term data beyond 2 years is limited. The main risks with extended use are metabolic: sustained GH elevation can worsen insulin sensitivity over time, and chronic IGF-1 elevation raises theoretical concerns about cancer risk (though this has not been observed in trials). Periodic blood work and medical supervision are advisable for any extended use. This is not medical advice.

References

  1. 1
    MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism(1997)PubMed ↗
  2. 2
    Two-year effects of ibutamoren (MK-677) on bone mineral density and body composition in healthy older adults(2008)PubMed ↗
  3. 3
    Oral administration of growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly(1999)PubMed ↗
  4. 4
    Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial(2008)PubMed ↗

Last updated: 2026-02-14