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AHuman RCT or meta-analysis
Cardiotoxic

MK-677

Ibutamoren · Nutrobal

MK-677 (ibutamoren, Nutrobal) is an orally active, non-peptide ghrelin-receptor (GHS-R1a) agonist that stimulates the body's own pulsatile growth hormone (GH) release and raises IGF-1. It is not an anabolic steroid and is not an approved drug anywhere; all human data come from Merck-era clinical trials in older adults and clinical populations, not in young healthy people using it for physique or performance. The main risks are that it reliably raises fasting blood glucose and worsens insulin sensitivity (a real diabetes-risk concern), causes fluid retention and lower-extremity edema, and a Phase IIb hip-fracture trial was terminated early for a congestive-heart-failure safety signal. It also modestly raises cortisol and prolactin and increases appetite. Because it drives GH/IGF-1 into a sustained elevated state, the theoretical long-term concerns of GH excess (edema, joint/carpal-tunnel symptoms, insulin resistance, and IGF-1-related proliferative risk) apply. There is no long-term safety data in healthy users. Anyone using it should treat rising glucose, edema, or breathlessness as reasons to stop and see a clinician.

Clinical readoutPED-adjacent · oral-gh-secretagogue
Hepatic strainLow
CardiovascularNone
HPTA suppressionLow
Half-life
24 h
Route
Oral
Evidence
A
Active
Once-daily oral dosing…
24 h2 d3 d4 d5 d
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Reported human elimination half-life is short (on the order of several hours); precise published half-life values are limited, but a single oral dose is pharmacokinetically mappable in plasma and once-daily oral dosing produces sustained 24-hour elevation of GH and IGF-1.
Pharmacology

Mechanism of action

MK-677 is a non-peptidyl mimetic of GH-releasing peptides that binds and activates the growth hormone secretagogue receptor (GHS-R1a), the endogenous ghrelin receptor, expressed in the pituitary and hypothalamic arcuate nucleus. Receptor engagement activates arcuate neuroendocrine neurons and amplifies pre-existing pulsatile GH secretion (increasing pulse amplitude and interpulse nadir rather than pulse frequency), which in turn raises hepatic IGF-1 and IGF-binding protein-3. Because it works through the physiologic GH axis, GH output remains subject to somatostatin feedback. As a ghrelin-receptor agonist it also stimulates appetite and modestly increases cortisol and prolactin secretion. Receptor and central-activation mechanisms are established in preclinical models; the downstream GH/IGF-1 rise is confirmed in human RCTs.
Kinetics

Pharmacokinetics

Half-life

Reported human elimination half-life is short (on the order of several hours); precise published half-life values are limited, but a single oral dose is pharmacokinetically mappable in plasma and once-daily oral dosing produces sustained 24-hour elevation of GH and IGF-1.

Active duration

Once-daily oral dosing sustains elevated 24-hour GH secretion and IGF-1 over days-to-weeks of continued use; IGF-1 rises within days and plateaus over 2-4 weeks. Relevant for washout/monitoring, not for evading testing.

Route

Oral (non-peptide, orally bioavailable; this is its defining feature versus injectable peptide secretagogues).

Metabolism & clearance

Cleared by hepatic metabolism; detailed human clearance and metabolite data are limited in the primary literature. No dedicated hepatic- or renal-impairment PK studies are available to guide dosing in organ dysfunction.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • Raises endogenous pulsatile GH secretion and increases serum IGF-1, restoring IGF-1 toward young-adult range in older subjects (human RCT).
  • Increases fat-free (lean) mass and body weight over months, without demonstrated gains in muscle strength or physical function in trials (human RCT).
  • Increases appetite (ghrelin-receptor effect), which typically attenuates over the first months (human RCT).
  • Reverses short-term diet-induced nitrogen wasting / improves nitrogen balance during caloric restriction (human RCT).
  • Improves sleep quality, increasing slow-wave (stage IV) and REM sleep in short-term studies (human RCT/crossover).
  • Increases markers of bone turnover (osteocalcin, urinary N-telopeptide); femoral-neck BMD effects were modest and site-limited (human RCT).
  • Did not produce meaningful improvements in functional performance, strength, or clinical outcomes in the populations studied (human RCTs).
Safety

Adverse effects by system

Cardiovascular

Congestive heart failure safety signal: a Phase IIb hip-fracture trial (25 mg/day) was terminated early due to CHF in a limited number of patients, and the authors concluded MK-677 had an unfavorable safety profile in that population. Fluid retention with transient lower-extremity edema is common. LDL cholesterol decreased modestly in one 2-year RCT. Long-term cardiovascular safety in healthy users is unknown.

Hepatic

No hepatotoxicity signal was reported in human RCTs up to 2 years, and MK-677 is not a 17-alpha-alkylated oral steroid. However, no dedicated hepatic-safety studies exist; liver risk is not well characterized in young healthy users.

Endocrine / HPTA

Acts on the GH/ghrelin (somatotropic) axis, not the hypothalamic-pituitary-gonadal axis; it is not known to suppress endogenous testosterone, LH, or FSH. It does modestly raise cortisol (in some studies) and prolactin (~23% in one study, remaining within normal range), and it sustains GH/IGF-1 elevation with the metabolic consequences of GH excess.

Reproductive

No direct human reproductive-outcome or fertility data. It is not a sex-steroid and is not established to suppress the gonadal axis; effects on fertility, pregnancy, and lactation are unstudied and it should be avoided in these settings.

Neuropsychiatric

No consistent serious psychiatric adverse effect reported in trials; effects on sleep architecture (increased slow-wave/REM sleep) are documented. Robust psychiatric safety data are lacking.

Renal

No direct nephrotoxicity reported, but GH-mediated sodium and fluid retention (edema) reflects renal fluid handling. No dedicated renal-safety or renal-impairment data are available, so renal safety in this population remains unstudied.

Hematologic

No clinically significant hematologic toxicity reported in the available human trials; hematologic parameters were not a highlighted safety concern. Dedicated hematologic data are limited.

Dermatologic

No specific dermatologic toxicity established in the human literature; data are essentially absent, so no reliable dermatologic effect can be stated.

Recovery

HPTA suppression & recovery

Suppression: Not a direct HPTA/gonadal suppressant - low expected effect on testosterone/LH/FSH

MK-677 works on the GH/ghrelin axis, not the hypothalamic-pituitary-gonadal axis, and is not established to suppress endogenous testosterone, LH, or FSH; therefore a SERM-based recovery protocol is generally not indicated for MK-677 alone, and it is not appropriate to start any SERM prophylactically for this compound. If MK-677 is used alongside androgens, that is a separate issue and any post-cycle management must be individualized. Because it does sustain GH/IGF-1 elevation and modestly raise cortisol and prolactin, and because endocrine effects are incompletely characterized, any concern about hormonal disruption or recovery should be evaluated with bloodwork and managed by a qualified endocrinologist rather than self-directed.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Fasting glucose and HbA1c (and consider fasting insulin / HOMA-IR) before and during use - highest-priority given documented hyperglycemia and insulin resistanceIGF-1 (to gauge degree of GH-axis stimulation)Lipid panelMorning cortisol and prolactin if symptomaticComprehensive metabolic panel including liver and renal functionBaseline and periodic blood pressure and weight/edema assessment

Cadence: Baseline before any use; recheck glucose/HbA1c and IGF-1 within the first 4-8 weeks and roughly every 3 months during continued use, with prompt rechecking if symptoms develop. Ongoing use should be under a clinician's supervision.

Warning signs — seek care
  • New or worsening shortness of breath, orthopnea, rapid weight gain, or leg/ankle swelling (possible heart failure / fluid overload) - stop and seek urgent care
  • Symptoms of high blood sugar (excessive thirst, frequent urination, fatigue, blurred vision)
  • New numbness/tingling or wrist pain (carpal tunnel-type symptoms of GH excess)
  • Persistent joint pain or muscle pain
  • Persistent edema that does not resolve
Do not use if

Contraindications

  • Diabetes mellitus or impaired glucose tolerance / prediabetes - MK-677 raises fasting glucose and reduces insulin sensitivity (excluded from trials for this reason).
  • Congestive heart failure or significant cardiac disease - CHF safety signal caused early trial termination.
  • Active or history of malignancy, or high cancer risk - sustained IGF-1 elevation is a theoretical proliferative concern; use is inadvisable.
  • Uncontrolled hypertension or edematous/fluid-overload states.
  • Pregnancy, breastfeeding, and use in adolescents/those still growing - no safety data.
  • Known acromegaly or active proliferative retinopathy.
  • Any condition where GH/IGF-1 elevation is undesirable; use only under medical supervision if at all.
Combinations

Interaction profile

  • MajorWith insulin: Metabolic / glucose
  • ModerateWith another GH secretagogue: Metabolic / glucose
  • ModerateWith growth hormone: Metabolic / glucose
  • ModerateWith IGF-1: Metabolic / glucose
  • ModerateWith a GLP-1 / incretin agonist: Metabolic / glucose
  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • This is not medical advice; MK-677 is not an approved drug and long-term safety in healthy users is unknown - the safest choice is not to use it, and any use should involve a clinician.
  • Get baseline bloodwork first (fasting glucose, HbA1c, IGF-1, lipids, metabolic panel) and repeat during use; do not use it if you are diabetic, prediabetic, or have insulin resistance.
  • Stop and seek medical care for shortness of breath, rapid weight gain, or leg swelling - a congestive-heart-failure signal caused a clinical trial to be halted.
  • Because it consistently raises blood sugar and reduces insulin sensitivity, monitor glucose closely and stop if glucose or HbA1c rises.
  • Avoid entirely with heart failure or cardiac disease, active or prior cancer, during pregnancy/breastfeeding, and in adolescents.
  • Do not start a SERM 'for MK-677' - it does not suppress the testosterone axis; any hormonal concern should be evaluated with labs and an endocrinologist, not self-managed.
  • Fluid retention, joint pain, and carpal-tunnel-type symptoms reflect GH excess and are reasons to reduce or stop and consult a clinician.
  • Report all supplements/drugs to your physician; product identity and purity of non-pharmaceutical material cannot be assumed.
Evidence

Citations (11)

Every clinical claim above is tied to a primary source. Overall evidence grade A — graded to the best available evidence for its core claims.

  1. 01

    MK-677 is an orally active ghrelin/GH-secretagogue receptor (GHS-R) agonist that amplifies pulsatile GH secretion.

    PreclinicalPMID 9092793 ↗

  2. 02

    MK-0677 activates hypothalamic arcuate nucleus neuroendocrine neurons, consistent with a central mechanism for stimulating GH release.

    PreclinicalPMID 9535057 ↗

  3. 03

    Daily oral MK-677 25 mg increased GH and IGF-1 into the young-adult range and increased fat-free mass over 12 months in healthy older adults, but did not improve strength or function; it increased body weight, appetite, caused transient lower-extremity edema and muscle pain, raised fasting glucose, decreased insulin sensitivity, and increased cortisol.

    RCTDOI 10.7326/0003-4819-149-9-200811040-00003 ↗

  4. 04

    In healthy elderly subjects, MK-677 dose-dependently raised 24-hour GH and IGF-1 and produced significant increases in fasting glucose (5.4 to 6.8 mmol/L at 4 weeks) and a ~23% rise in prolactin within the normal range; cortisol did not change.

    RCTDOI 10.1210/jcem.81.12.8954023 ↗

  5. 05

    In a Phase IIb hip-fracture RCT (25 mg/day), the trial was terminated early due to a congestive heart failure safety signal and MK-0677 was judged to have an unfavorable safety profile despite raising IGF-1.

    RCTDOI 10.1016/j.archger.2010.10.004 ↗

  6. 06

    In a hip-fracture RCT, MK-0677 raised IGF-1 by ~84% but produced no statistically significant improvement in functional performance; diabetics and CHF patients were excluded.

    RCTDOI 10.1111/j.1532-5415.2004.52156.x ↗

  7. 07

    MK-677 reversed short-term diet-induced negative nitrogen balance and raised IGF-1/IGFBP-3 in caloric-restricted healthy volunteers.

    RCTDOI 10.1210/jcem.83.2.4551 ↗

  8. 08

    Prolonged oral MK-677 improved sleep quality, increasing slow-wave (stage IV) and REM sleep in young and older adults.

    RCTDOI 10.1159/000127249 ↗

  9. 09

    MK-677 increased bone-turnover markers (osteocalcin, urinary N-telopeptide) and modestly increased femoral-neck BMD (site-limited) in postmenopausal women.

    RCTDOI 10.1210/jcem.86.3.7294 ↗

  10. 10

    MK-677 is orally bioavailable and its plasma pharmacokinetic time-course is mappable after a single oral dose.

    PreclinicalDOI 10.1016/s0378-4347(97)00035-2 ↗

  11. 11

    MK-677 is not an approved therapy; GH/GH-secretagogue use in aging remains unproven and controversial, with heart failure among noted concerns.

    ReviewPMID 20518193 ↗

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice