MK-677
Research OnlyAn orally-active, non-peptide growth hormone secretagogue that mimics ghrelin's effects on GHS-R1a. While not technically a peptide, it is frequently researched alongside peptides for its sustained IGF-1 elevation. Completed Phase 2 trials for muscle wasting, sleep, and bone density. Not FDA approved; WADA prohibited.
Ibutamoren · Ibutamoren Mesylate · L-163,191 · Nutrobal
18 human studies
- Preclinical
- 29%
- Clinical
- 43%
Based on 42 cited sources
clinically demonstrated · moderate confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 70: 1A=30 (>=2 independent double-blind placebo-controlled RCTs — Chapman 1996 8954023, Nass 2008 2-yr 18981485, Bach hip-fracture n=161 15066065, Copinschi 9349662/8768828, Svensson 9661080 — but no meta-analysis/systematic review of RCTs found); 1B=16 (>=1 low-RoB DB-RCT, no high-confidence AMSTAR-2 review); 1C=9 (cumulative human N ~300-1,000 across 18 human studies); 1D=9 (right population/route but primary endpoints largely surrogate — IGF-1/body-comp; functional endpoints failed in Bach); 1E=6 (substantial multi-study preclinical incl. receptor cloning). Mechanism 88: 2A=35 (GHS-R1a cloned and MK-677 confirmed full agonist with binding + functional response, Howard 1996 8688086); 2B=27 (full Gq/11-PLC-Ca2+ -> GH exocytosis -> hepatic IGF-1 chain mapped); 2C=16 (dose-response in humans 8954023 and animals, in vivo); 2D=10 (confirmed in-vivo mammalian/human). Plausibility 81: 3A=28 (mechanism->IGF-1 surrogate firmly established, surrogate->clinical benefit inferred — robust IGF-1 rise but functional gains non-significant); 3B=24 (coherent with GH/IGF-1 axis physiology); 3C=18 (multiple same-class secretagogues — ghrelin, GHRPs — reliably raise GH); 3D=11 (moderately broad: sleep, body-comp, bone, anti-aging). Global Coverage 71: 4A=27 (replicated by independent groups — Virginia, Brussels, Goteborg, Merck multi-site); 4B=21 (Bach 15066065 was a 7-country multicenter trial; literature spans USA/Belgium/Sweden/Denmark/UK and more); 4C=18 (~42 studies, diverse contexts); 4D=5 (reached Phase 2 / clinical-trial registration, never approved). Community Experience 74: 5A=27 (large documented use across r/Peptides and fitness venues); 5B=23 (>7 years sustained real-world use); 5C=16 (broadly consistent themes — sleep, appetite, water retention); 5D=8 (isolated/minor recurring signals — glucose intolerance, edema, lethargy — no dominant serious-AE pattern). Effectiveness clinical 42 (moderate confidence): human DB-RCTs show robust IGF-1 restoration to young-adult range and modest fat-free-mass gain (~+1.1 kg, Nass 18981485) but functional/clinical endpoints failed to reach significance (Bach 15066065) and most demonstrated effects are on surrogate markers — E1=16, E2=10, E3=6, E4=10.
MK-677 is a non-peptide ghrelin receptor agonist with extensive human clinical trial data. Unlike injectable peptide secretagogues, it offers oral bioavailability and sustained 24-hour effects.
How It Works (Simplified)
MK-677 mimics ghrelin to stimulate growth hormone release through four key pathways:
Binds to ghrelin receptor on pituitary somatotrophs, triggering calcium-mediated GH vesicle release without affecting pulse frequency.
Hepatic IGF-1 synthesis remains elevated for 24+ hours, providing sustained anabolic signaling unlike short-acting peptide secretagogues.
Hypothalamic receptor activation modulates sleep architecture, increasing REM and Stage 4 deep sleep by up to 50%.
~60-65% absorbed through GI tract, surviving stomach acid unlike peptides. Single daily dose maintains effect for 24 hours.
Key Research: Chapman IM et al. demonstrated dose-dependent GH elevation restoring IGF-1 to young adult levels in elderly subjects. PMID:8954023
Important Limitations
- Not a peptide - Small molecule spiroindoline compound, included due to same receptor target as GHRP-6/Ipamorelin
- Development discontinued after Phase 2 despite positive results - commercial rather than safety reasons
- Increases appetite via ghrelin pathway (may be unwanted)
- Mild glucose/insulin effects require monitoring in pre-diabetic individuals
- WADA prohibited in all sports; detectable via mass spectrometry
Reported positives
- Improved sleep quality consistently reported
- Increased appetite beneficial for muscle gain goals
- Improved skin quality and hair growth noted
- Oral administration preferred over injectable alternatives
Reported negatives
- Significant water retention and bloating common
- Increased blood glucose and insulin resistance reported
- Lethargy and fatigue especially at higher amounts
- Joint pain from water retention in some users
“Widely discussed in r/Peptides and fitness forums. Oral convenience is a major draw.”
Self-reported, unverified accounts — not clinical evidence and no substitute for the cited research. Anecdotes are prone to selection bias and placebo effects.
Rapid IGF-1 elevation begins within days of first dose. Human studies show measurable GH increases after single dose. Sleep quality improvements (increased REM and Stage 4 deep sleep) often reported within first week. Increased appetite common due to ghrelin pathway activation.
PMID:9349662IGF-1 levels continue to rise toward young adult reference range. Water retention and mild joint fullness may occur. Improved recovery and sleep quality typically noticeable. Appetite stimulation persists.
PMID:8954023Steady-state IGF-1 elevation achieved. Body composition changes (increased lean mass, possible fat reduction) may become measurable. Continued sleep architecture improvements. Monitor fasting glucose in susceptible individuals.
PMID:9661080Long-term studies (up to 2 years) show sustained IGF-1 elevation and bone mineral density improvements. Body composition benefits continue. Glucose/insulin effects require ongoing monitoring. No tachyphylaxis observed in clinical trials.
PMID:18981485Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
CJC-1295
SynergisticMK-677 (ghrelin mimetic) combined with CJC-1295 (GHRH analog) may produce synergistic GH release through dual pathway activation - similar to GHRP+GHRH synergy.
Sermorelin
SynergisticGHRH analog (sermorelin) plus GHS-R1a agonist (MK-677) may synergistically enhance GH release through complementary signaling pathways.
Tesamorelin
SynergisticSimilar to sermorelin - GHRH+GHS dual pathway activation may amplify GH response compared to either alone.
Ipamorelin
CautionBoth act on GHS-R1a receptor. MK-677's 24-hour action may make additional GHRP peptides redundant. Consider potential receptor saturation.
GHRP-6
CautionBoth are ghrelin receptor agonists. MK-677's sustained action overlaps with GHRP-6's pulsatile effects - combining may be redundant rather than synergistic.
GHRP-2
CautionSimilar mechanism overlap as GHRP-6. MK-677's oral convenience and 24-hour duration often makes it preferred over injectable GHRPs rather than combined.
AOD-9604
CautionMK-677 elevates endogenous GH while AOD-9604 is a non-functional GH fragment. Combining active GH stimulation with failed GH fragment lacks scientific rationale.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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