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Research peptide — not a dietary supplement
MK-677 is a research compound, not a regulated dietary supplement. It is typically administered by injection and sold “for research use only.” The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
Most MK-677 studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 1996–2018 with a typical study size of 26 participants.
Based on 13 studies · 9 RCTs · 895 total participants
Confidence
ModerateBy outcome
MK-677 has an evidence score of 3/10 — emerging evidence based on 13 indexed studies. An orally-active, non-peptide ghrelin mimetic (growth-hormone secretagogue) grouped with the GH-secretagogue peptides. Honest appraisal: real human RCTs show it reliably raises GH and IGF-1 and modestly increases fat-free mass — but the trials that tested whether that translates into real clinical benefit FAILED. It did not improve strength or physical function in healthy elderly, did not slow Alzheimer's (n=563), and the hip-fracture-recovery trial was stopped early for a heart-failure safety signal. It is an investigational drug Merck never brought to market, not a regulated supplement, and it is banned in sport. Representative study: PMID 18981485.
The commonly studied dose of MK-677 is No endorsed human dose. The Merck trials used 25 mg orally once daily; that is reported here for context only — MK-677 is an investigational drug and unregulated grey-market product, not a supplement to dose.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Semaglutide
Mostly mechanism / observationalAn FDA-approved GLP-1 receptor agonist (Ozempic/Rybelsus for type 2 diabetes, Wegovy for chronic weight management) with genuinely strong, large-RCT evidence for glycemic control and substantial weight loss, plus a cardiovascular-outcomes benefit. Honest appraisal: this is a real prescription medicine with real efficacy AND real risks — a boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and growing concern about grey-market/compounded versions. It is included here for reference only, not as a supplement and not auto-recommended.
Last reviewed June 2026 · evidence from 13 studies · how we score
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
MK-677 (Ibutamoren)
An orally-active, non-peptide ghrelin mimetic (growth-hormone secretagogue) grouped with the GH-secretagogue peptides. Honest appraisal: real human RCTs show it reliably raises GH and IGF-1 and modestly increases fat-free mass — but the trials that tested whether that translates into real clinical benefit FAILED. It did not improve strength or physical function in healthy elderly, did not slow Alzheimer's (n=563), and the hip-fracture-recovery trial was stopped early for a heart-failure safety signal. It is an investigational drug Merck never brought to market, not a regulated supplement, and it is banned in sport.
Real human RCTs reliably show MK-677 raises GH/IGF-1 and modestly increases fat-free mass, but its pivotal trials failed to deliver strength, cognitive, or recovery benefit and surfaced metabolic and cardiac risks.
MK-677 (ibutamoren, ibutamoren mesylate; development code L-163,191 / MK-0677) is an orally-active, non-peptide small molecule that mimics the gut hormone ghrelin by agonizing the growth-hormone-secretagogue receptor (GHS-R1a) on the pituitary and hypothalamus.
Although it is chemically a spiroindoline, not a peptide, it is universally grouped with the GH-secretagogue peptides (GHRP-6, ipamorelin, CJC-1295) in the research-compound space, so it is filed here under that category.
Its defining property is genuine and well-replicated in real human RCTs: a single daily oral 25 mg dose enhances pulsatile GH secretion and raises serum IGF-1 — in healthy elderly subjects it restores IGF-1 into the young-adult range (Chapman 1996), and across populations it raises IGF-1 by roughly 40-75%.
Where honesty matters is the gap between that reliable biomarker effect and actual clinical benefit. Merck developed MK-677 in the 1990s-2000s as a candidate for sarcopenia/frailty, catabolic wasting, Alzheimer's disease, and hip-fracture recovery, and ran several real, well-powered placebo-controlled trials.
The biomarker story held up; the clinical story did not.
In the landmark 2-year Annals of Internal Medicine RCT in healthy older adults (Nass 2008), MK-677 raised GH/IGF-1 and increased fat-free mass by ~1.1 kg vs placebo — but that gain produced NO improvement in strength or physical function, and it came with raised fasting glucose, decreased insulin sensitivity, increased appetite, transient lower-extremity edema, muscle pain, and raised cortisol.
The 12-month Alzheimer's trial (Sevigny 2008, n=563) confirmed target engagement (IGF-1 rose ~73%) yet was flatly negative on every cognitive and functional endpoint.
The phase-IIb hip-fracture trial (Adunsky 2011, n=123) raised IGF-1 but failed most functional-recovery measures and was terminated early for a congestive-heart-failure safety signal, which the authors called 'an unfavorable safety profile in this patient population.' So the realistic picture is a compound that reliably does what it says to GH/IGF-1, but whose body-composition and clinical promise repeatedly failed to translate into proven benefit — and which carries real metabolic and cardiovascular concerns.
Merck discontinued development; it has never been approved anywhere. Today essentially all human consumption is via unregulated grey-market 'research-use-only' product of unverified purity, and it is on the WADA Prohibited List (GH secretagogues, banned at all times).
Overall evidence for a meaningful human benefit is weak/emerging despite the existence of real RCTs.
An orally-active non-peptide spiroindoline that binds and activates the growth-hormone-secretagogue receptor (GHS-R1a) — the same receptor as the natural hormone ghrelin — on pituitary somatotrophs and in the hypothalamus. It is a ghrelin mimetic, confirmed against the cloned GHS-R.
Amplifies pre-existing pulsatile GH release (via several mechanisms including reduced somatostatin tone and amplified GHRH signaling) rather than creating new pulses. In humans this raises 24-h mean GH and downstream IGF-1 — the core, RCT-replicated pharmacodynamic effect.
Sustained GH elevation raises hepatic IGF-1 and IGF-binding proteins. Real human RCTs show 40-75% IGF-1 increases. This is reliable target engagement — but in Merck's trials it did NOT translate into improved cognition (Alzheimer's), strength/function (elderly), or recovery (hip fracture).
Because it mimics ghrelin (the 'hunger hormone'), MK-677 stimulates appetite — a consistent finding in human trials. This drives some of the weight/lean-mass change and is also why it has been explored in catabolic/wasting states.
How MK-677 works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Tap node to isolate • Pinch to zoom • Tap edge for research
No endorsed human dose. The Merck trials used 25 mg orally once daily; that is reported here for context only — MK-677 is an investigational drug and unregulated grey-market product, not a supplement to dose.
Can be taken without food
| Form | Type |
|---|---|
| 💊None (investigational compound, not for human use) | Recommended |
There is no recommended consumer form. MK-677 is an investigational drug Merck never marketed and a WADA-prohibited substance, not a dietary supplement.
Minimum: 4 weeks
Optimal: 12 weeks
Cycling: Not required
Note: Trials dosed once daily (some at bedtime, to align with the nocturnal GH pulse). No timing is endorsed here — there is no approved human use, and any consumption is off-label / grey-market.
Dose-response data unavailable. The current published research for MK-677 does not provide sufficient dose-specific outcome data to generate reliable dose-response curves.
Refer to the Dosage & Timing section above for recommended dose ranges based on available evidence.
Reliably increases pulsatile GH and serum IGF-1 in humans — IGF-1 up ~40-75% across trials, restored to young-adult range in healthy elderly. The best-evidenced effect.
Increases fat-free mass (~1.1 kg vs placebo over 1 year), but in the controlled trial this did NOT improve strength or physical function. Anabolic on paper, not on performance.
Despite target engagement, MK-677 did NOT slow Alzheimer's (n=563) and FAILED most functional-recovery measures after hip fracture — two well-powered RCTs that came up negative.
GH elevation worsens glucose control: trials consistently showed raised fasting glucose, decreased insulin sensitivity, and impaired oral glucose tolerance.
Expected GH/ghrelin effects: lower-extremity edema, water retention, muscle/joint discomfort, raised cortisol, and a marked increase in appetite (often the most-reported effect).
Contraindicated — never studied; GH/IGF-1-axis manipulation is inappropriate in pregnancy.
Avoid — sustained IGF-1 elevation is theoretically growth-promoting.
Avoid — MK-677 reliably raised fasting glucose and reduced insulin sensitivity in trials.
Caution — a CHF safety signal stopped the frail-elderly hip-fracture trial early; fat-free-mass gains did not translate into strength or function.
Prohibited at all times under the WADA Prohibited List (GH secretagogues).
MK-677 raises GH, which antagonises insulin and raised fasting glucose / reduced insulin sensitivity in every trial — it can worsen glycemic control and oppose glucose-lowering therapy.
Stacking with GH or other secretagogues (GHRP-6, ipamorelin, CJC-1295) compounds GH-axis side effects — edema, insulin resistance, raised cortisol — with no evidence of added benefit.
Tip: Expected ghrelin-mimetic effect; often subsides over a few months. Manage intake; discontinue if unwanted.
Tip: Monitor glucose; avoid in diabetes/prediabetes. A consistent finding across the RCTs.
Tip: Expected GH-axis effect; typically transient. Reduce or discontinue.
Tip: Common GH-axis effect; generally transient.
Tip: Modest rise observed in the long-term trial; clinical significance uncertain.
Timing is flexible for MK-677 — consistent daily use matters more than the time of day. The clinical trials used a fixed oral 25 mg once-daily regimen (its key advantage over injectable secretagogues is oral activity).
MK-677 should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are increased appetite, reduced insulin sensitivity / raised fasting glucose, water retention / lower-extremity edema. Use caution if any of these apply to you: Pregnancy and breastfeeding (contraindicated — never studied, GH/IGF-1-axis effects); Active or prior malignancy (IGF-1 elevation is theoretically growth-promoting); Diabetes / impaired glucose tolerance (MK-677 raises fasting glucose and reduces insulin sensitivity).
Tirzepatide
Mostly mechanism / observationalAn FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for obesity and obstructive sleep apnea), not a dietary supplement. Honest appraisal: in head-to-head phase-3 trials it is the most effective approved weight-loss drug to date — up to ~21% body-weight loss over 72 weeks and superior to semaglutide — but it is a real medicine with real risks: a boxed warning for thyroid C-cell tumors, common GI side effects, and pancreatitis/gallbladder signals. Do not source or use it outside a prescription.
GH-driven fluid retention and the observed congestive-heart-failure signal mean caution alongside anything that stresses fluid balance or cardiac function, especially in older or cardiac patients.
Tip: A CHF safety signal in frail elderly hip-fracture patients led to early trial termination. Avoid in anyone with cardiac risk.