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Non-peptide ghrelin mimetic (small molecule)

MK-677 (Ibutamoren)

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

Tier 2 — Human observationalReviewed 2026-05-04

Orally bioavailable small molecule that elevates GH and IGF-1. Multiple human RCTs confirm the hormone effect; clinical-outcome benefits are far less settled.

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Overview

MK-677 is a non-peptide, orally active growth hormone secretagogue developed by Merck in the 1990s. It is structurally a spiro-piperidine, not a peptide — it is included in this library because users overwhelmingly stack it alongside peptides like ipamorelin and CJC-1295. Multiple human RCTs in older adults consistently demonstrate sustained elevations in GH and IGF-1 with daily oral dosing. Clinical-outcome evidence (functional strength, fall reduction, fat loss, sleep) is weaker and inconsistent, and the most-cited large trial in older adults at risk of fracture (Adunsky 2011) did not reduce fall-related fractures.

Mechanism

Selective agonist at the growth hormone secretagogue receptor (GHSR-1a) — the endogenous ghrelin receptor. Mimics ghrelin's signal at the pituitary and hypothalamus, driving pulsatile GH release and downstream IGF-1 elevation. Also drives appetite and may elevate cortisol and prolactin modestly. Not a GHRH analog; mechanism is parallel to ipamorelin and GHRP-2/6, but oral and small-molecule.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Elevation of GH and IGF-1

Tier 2high confidence

Multiple RCTs (Chapman 1996, Murphy 1998, Nass 2008) consistently demonstrate sustained 1.5–2x increases in IGF-1 with 12+ months of daily oral dosing in older adults. The hormonal effect is well established. Tier 2 because the studies are mostly small-to-mid sized and the indication of interest (raising IGF-1 as a goal in itself) doesn't have a regulator-approved bar to clear.

Chapman IM et al. 1996Nass R et al. 2008

Body composition (fat-free mass) in older adults

Tier 2high confidence

Nass et al. (Annals of Internal Medicine 2008, n=65, 12 months) reported a ~1.1 kg increase in fat-free mass vs placebo in healthy older adults, without significant strength or function improvement. Modest effect, single trial of this size.

Nass R et al. 2008

Hip-fracture functional recovery in elderly

Tier 2high confidence

Adunsky et al. (Arch Gerontol Geriatr 2011, n=181) tested MK-677 vs placebo in elderly post-hip-fracture patients. The trial did not show reduction in fall-related fractures and the functional benefit was modest. Reported here to set expectations honestly — the evidence does exist, and it is mixed.

Adunsky A et al. 2011

Sleep quality

Tier 3medium confidence

Small studies report increases in stage-IV slow-wave sleep and REM duration. No large RCT with sleep as the primary clinical endpoint. Plausible mechanism (GH/ghrelin sleep effects) but indication-specific human evidence is thin.

Copinschi G et al. 1996

Body composition in young/healthy lifters (recreational use)

Tier 3high confidence

Recreational use is widespread but not directly studied. Generalizing the older-adult body-composition data to young lifters with a confounded resistance-training stimulus is not supported by trial evidence specific to that population.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

10,000–25,000 mcgonce daily · oral

Studied human doses cluster at 10 mg or 25 mg per day. Note the unit math: 25 mg = 25,000 mcg. Most commercial 'research' MK-677 is sold as a liquid solution; concentration varies by vendor — verify and re-calculate every batch.

Contraindications

  • Active malignancy (theoretical concern from sustained IGF-1 elevation)
  • Heart failure or significant fluid-overload risk (water retention, edema reported)
  • Uncontrolled diabetes or glucose intolerance (worsens insulin resistance and fasting glucose)
  • Pregnancy and breastfeeding
  • Adolescents with open growth plates (use only under endocrinology supervision)
  • Concomitant use with hormones or appetite stimulants without supervision

Reported side effects

  • Increased appetite (often significant; this is a ghrelin-receptor-driven on-target effect)
  • Water retention, peripheral edema, mild puffiness
  • Increased fasting glucose and insulin resistance
  • Reduced glucose tolerance (clinically meaningful in some users; check fasting glucose / HbA1c)
  • Lethargy, vivid dreams, increased sleep duration
  • Mild cortisol and prolactin elevation in some studies
  • Numbness or paraesthesia (rare; consistent with high-IGF-1 carpal-tunnel-like effects)

Reconstitution & storage

MK-677 is orally active and not reconstituted. Sold by research vendors as either capsules or a liquid suspension (commonly 25 mg/mL). At 25 mg/mL, a 10 mg dose is 0.4 mL. Liquid solutions are often dosed via graduated dropper rather than a syringe. Identity, purity, and concentration of research-vendor product vary widely — third-party assay if relying on it for dosing accuracy.

Storage. Store the manufacturer/vendor product as labeled. Liquid solutions: typically refrigerate; protect from light. Capsules: room temperature, dry.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

DRAFT — pending Wayne's review. MK-677 is the entry where 'not a peptide' matters most editorially — it's a small molecule, not a GHRP, and the class field reflects that explicitly. The hormone-elevation evidence is real (Tier 2), but the leap from 'IGF-1 went up' to 'you'll get jacked / live longer / sleep better' is exactly the kind of mechanism-as-evidence move our tier framework is designed to push back on. Flag the Adunsky null result honestly — most consumer write-ups omit it.

Citations

  1. [1]
    Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects
    Chapman IM, Bach MA, Van Cauter E, et al. · Journal of Clinical Endocrinology & Metabolism · 1996 · PMID 8636336
    Foundational Tier 2 evidence for sustained GH/IGF-1 elevation with oral dosing.
    View source
  2. [2]
    Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial
    Nass R, Pezzoli SS, Oliveri MC, et al. · Annals of Internal Medicine · 2008 · PMID 19075203
    Largest mid-duration RCT of MK-677 in older adults; anchor for the body-composition indication.
    View source
  3. [3]
    MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study
    Adunsky A, Chandler J, Heyden N, et al. · Archives of Gerontology and Geriatrics · 2011 · PMID 21620503
    Largest published clinical-outcome RCT; reports a null result on the primary fracture endpoint.
    View source
  4. [4]
    Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men
    Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, et al. · Journal of Clinical Endocrinology & Metabolism · 1996 · PMID 9415432
    Short-term GH profile and sleep architecture data; supports the Tier 3 sleep claim.
    View source