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Growth Hormone Axis

MK-677 (Ibutamoren)

Oral ghrelin mimetic that raises GH and IGF-1 for 24 hours; well studied in humans, with appetite and blood-sugar trade-offs.

InvestigationalEvidence level 4 of 5: Human RCTs or approved abroadAlso: Ibutamoren, Ibutamoren mesylate, MK-0677, L-163,191, LUM-201

Overview

MK-677 (ibutamoren) is an orally active, non-peptide molecule that activates the ghrelin receptor, producing sustained increases in growth hormone and IGF-1 from a single daily dose. Merck developed it in the 1990s for growth hormone deficiency, frailty and recovery after hip fracture. Human trials consistently show higher IGF-1, increased lean mass and deeper slow-wave sleep. They also show the main liabilities: increased appetite, fluid retention, and rising fasting glucose and insulin resistance. It is not approved anywhere and is sold online as a 'research chemical', often with uncertain purity. Use only with careful metabolic monitoring.

Classification
Oral non-peptide (spiropiperidine) ghrelin receptor agonist / growth hormone secretagogue
Route
Oral
Half-life
~4–6 hours (oral); GH/IGF-1 effect lasts ~24 hours

Mechanism of action

Primary targetGhrelin receptor (GHSR-1a), pituitary and hypothalamus
  1. Oral absorptionWell absorbed by mouth; long duration allows once-daily dosing.
  2. Activates GHSR-1aMimics ghrelin at pituitary and hypothalamic receptors.
  3. Amplifies GH pulsesIncreases GH pulse amplitude and suppresses somatostatin tone.
  4. Sustained IGF-1 riseIGF-1 rises roughly 40–60% and stays elevated with daily use.
  5. Hunger signalingGhrelin-receptor activation also increases appetite and food intake.
Downstream effects
  • Higher GH and IGF-1
  • Increased fat-free mass
  • Deeper slow-wave sleep
  • Increased appetite

Researched for

  • Age-related GH decline and frailty
  • Hip-fracture recovery
  • Pediatric growth hormone deficiency
  • Sarcopenia
  • Sleep architecture

Research notes

  • 2-year RCT in healthy older adults (Nass 2008): IGF-1 rose to young-adult levels and fat-free mass increased, but strength and function did not improve.
  • Fasting glucose and insulin resistance worsened in several trials; appetite increase and edema were common.
  • A hip-fracture recovery RCT (Adunsky 2011) was stopped early; a numerical excess of heart-failure events was observed.
  • Small studies show increased slow-wave and REM sleep in young and older adults.

Reported side effects

  • Increased appetite
  • Water retention and edema
  • Rising fasting glucose / insulin resistance
  • Lethargy
  • Joint or muscle aches; hand numbness

Contraindications & cautions

  • Diabetes or prediabetes (relative)
  • Heart failure
  • Active malignancy
  • Pregnancy or breastfeeding
  • Uncontrolled hypertension

Lab monitoring

  • Fasting glucose, HbA1c, fasting insulin
  • IGF-1
  • Lipid panel
  • CBC and CMP
  • Blood pressure, weight, waist

Dosing and pricing for MK-677 (Ibutamoren)

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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