MK-677
| Category | Growth Hormone Secretagogues |
| Goals | Muscle & Performance · Recovery · Sleep |
| Evidence level | Clinical — multiple completed Phase 2 trials (raises GH/IGF-1, lean mass; no approval) |
| Legal status | Research-only — not approved for human use |
| FDA status | Not approved; investigational, development discontinued |
| Half-life | ~24 hours (once-daily oral) |
| Routes | Oral (orally bioavailable) |
| CAS / MW / Structure | 159752-10-0 · 528.66 g/mol · non-peptide spiropiperidine |
| Last reviewed | 2026-06-07 |
In one line
An orally active, non-peptide ghrelin mimetic that raises GH and IGF-1 with once-daily dosing — the most clinically studied compound in this category, but never approved and a WADA-banned investigational drug.
Evidence at a glance
MK-677 is unusual here: it has completed human clinical trials (up to 2 years) showing it reliably raises GH/IGF-1 and increases lean (fat-free) mass — but trials also found no strength/function benefit and worsened insulin sensitivity / glucose tolerance, and it was never approved. See Evidence Grading Explained and the Disclaimer.
Key Takeaways
- A non-peptide spiropiperidine that mimics ghrelin at GHS-R1a, stimulating pulsatile GH and downstream IGF-1.
- Orally active with a ~24 h half-life — the only GH secretagogue here taken as a pill, dosed once daily.
- Clinically demonstrated to raise IGF-1 and increase fat-free mass (Nass 2008: +1.5 kg vs −0.5 kg placebo over 12 months), but with no functional/strength gain and increased insulin resistance.
- Best-known side effects: increased appetite, water retention/edema, and reduced insulin sensitivity / higher fasting glucose.
- Not FDA-approved (development discontinued) and WADA-prohibited in and out of competition.
What Is It
MK-677 (ibutamoren; originally MK-0677 / L-163191, marketed in grey channels as “Nutrobal”) is a synthetic, orally bioavailable, non-peptide growth-hormone secretagogue. Unlike the injectable peptides in this category, its spiropiperidine scaffold resists gut proteases, so it survives oral administration. It acts as a ghrelin mimetic — binding the same receptor as the hormone ghrelin — and was developed (originally by Merck) as a potential treatment for conditions involving GH deficiency, frailty, and muscle wasting.
Mechanism of Action
- GHS-R1a (ghrelin-receptor) agonism (established mechanism) — activates the ghrelin receptor on pituitary somatotrophs and in the hypothalamus, driving pulsatile GH release and hepatic IGF-1 synthesis.
- Oral bioavailability (established) — the non-peptide structure confers resistance to GI breakdown, enabling once-daily oral dosing.
- Sustained 24-h elevation (clinical PK) — its long half-life produces a durable rise in GH/IGF-1 across the day, distinct from the brief pulse of injectable GHRPs.
Not a "peptide" in the usual sense
Despite living in a peptide wiki by association, MK-677 is a small non-peptide molecule, not an amino-acid chain. Its ghrelin-mimetic action is what places it in the GH-secretagogue family.
Evidence by Outcome
| Outcome | Evidence | Notes |
|---|---|---|
| Raises GH / IGF-1 | Clinical | Consistent across trials; sustained over 12+ months (Nass 2008) |
| Increases fat-free mass | Clinical | +1.5 kg vs −0.5 kg placebo over 12 months (largely body water/lean mass) |
| Strength / physical function | Clinical (negative) | No improvement in strength or function in the 12-month trial |
| Bone density | Clinical | Studied; modest/mixed effects in older adults |
| Sleep quality | Preclinical / Clinical | Reported increases in REM/slow-wave sleep in some studies |
| Insulin sensitivity / glucose | Clinical (adverse) | Increased insulin resistance and reduced glucose tolerance |
| Appetite / body weight | Clinical | Reliably increases appetite (ghrelin-mimetic effect) |
Reported Dosing
Not medical advice
Protocols as reported in community sources and the clinical literature. There is no approved therapeutic dose. See Reconstitution & Dosing Math.
| Route | Dose (reported) | Frequency | Notes |
|---|---|---|---|
| Oral | 25 mg/day (the dose used in the Nass 2008 trial) | Once daily | Often taken before bed (sleep/appetite timing) |
| Oral (community) | ~10–25 mg/day | Once daily | Lower doses used to limit water retention/appetite |
Pharmacokinetics
MK-677’s ~24-hour half-life supports once-daily oral dosing and produces a sustained GH/IGF-1 elevation rather than a discrete pulse. Oral bioavailability is its defining practical advantage over injectable GHRPs and GHRH analogs. See Half-Life & Pharmacokinetics.
Side Effects & Risks
- Increased appetite — a direct, expected ghrelin-mimetic effect; can drive weight gain.
- Water retention / edema and muscle/joint aches are commonly reported, consistent with GH elevation.
- Reduced insulin sensitivity and higher fasting glucose were documented in controlled trials — a meaningful metabolic concern, especially for those with diabetes risk; glucose/HbA1c monitoring is prudent.
- Lethargy and mild transaminase changes have been reported in some users/studies.
- No proven functional benefit despite lean-mass gain — the risk/benefit picture in healthy people is unfavorable.
- Sourcing risk: sold as a research chemical (often liquid or capsule); identity and dose accuracy vary. See Sourcing, Red Flags & Scams, Bloodwork & Monitoring, Side Effects & Risk Management.
Cycling
Community protocols commonly run MK-677 for 8–16 weeks (sometimes longer, given oral convenience) with breaks, partly to manage water retention and monitor glucose/IGF-1. No evidence-based cycling standard exists. See Cycling.
Stacks It Appears In
- Often used standalone (oral convenience) for GH/IGF-1 elevation.
- Combined with injectable GH secretagogues like CJC-1295 + Ipamorelin for an oral + pulse approach.
- Appears in bodybuilding “GH support” stacks alongside SARMs/AAS in grey-market use.
Comparisons
- MK-677 vs Ipamorelin — both are ghrelin-receptor agonists, but MK-677 is oral, long-acting (~24 h) vs Ipamorelin’s short injectable pulse.
- vs CJC-1295 — CJC-1295 is a GHRH analog (different receptor); MK-677 is a ghrelin mimetic.
- vs Hexarelin — Hexarelin is an injectable, less-selective GHRP; MK-677 is the oral, more sustained option.
Sourcing & Quality
Sold as a research chemical in capsule or liquid form; concentration and identity are not guaranteed, and underdosing/overdosing is common. Evaluate quality before trusting a product: How to Read a CoA, Sourcing, Red Flags & Scams. Storage: Storage & Handling. No vendors are endorsed here.
Legal & Regulatory Status
(As of 2026-06-05.) Not FDA-approved for any use; it is an investigational drug whose development was discontinued and is sold only as an unapproved research chemical (not a legal dietary supplement despite “Nutrobal” branding). It is explicitly prohibited by WADA in and out of competition as a GH secretagogue / ghrelin mimetic (Section S2). Status varies by country. See Regulatory & Legal Status.
FAQ
Is MK-677 a steroid or a SARM? Neither. It is a ghrelin mimetic / GH secretagogue. It is often grouped with SARMs in grey-market sales but works through a different (GH/IGF-1) pathway.
Is MK-677 FDA-approved? No. It completed clinical trials but was never approved; development was discontinued.
Is it banned in sport? Yes — WADA prohibits GH secretagogues including MK-677 both in and out of competition.
What’s the main downside? Trials showed increased insulin resistance / impaired glucose tolerance and no strength/function benefit, alongside appetite and water-retention effects.
Injection or oral? Oral — that’s its key distinction from the injectable peptides in this category.
References
- Nass R. et al. (2008). “Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.” Annals of Internal Medicine, 149(9):601–611.
- Patchett A.A. et al. (1995). “Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.” PNAS, 92(15):7001–7005.
- Murphy M.G. et al. — clinical pharmacology and IGF-1 effects of MK-677 in healthy and GH-deficient adults.
- Sigalos J.T., Pastuszak A.W. (2017). “The safety and efficacy of growth hormone secretagogues.” Sexual Medicine Reviews (PMC5632578).
- WADA (2026). Prohibited List, Section S2 (peptide hormones, growth factors, related substances and mimetics).
← Growth Hormone Secretagogues · Home Educational information only — not medical advice. See Disclaimer.