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MK-677

Tier 1 · Human trials
Also known as Ibutamoren · MK-0677 · Nutrobal

Multiple double-blind, randomized, placebo-controlled human trials exist (healthy volunteers, GH-deficient adults, elderly and hip-fracture patients, including the pivotal 2-year Nass et al. 2008 trial). Human RCT-grade data support GH/IGF-1 elevation and body-composition effects. However, functional-outcome endpoints repeatedly failed and Merck discontinued development; certain PK, sleep, and combination-use claims rest on lower-tier or single sources.

Half-life
~6 h
Routes
Oral · Intravenous · Subcutaneous · Intranasal
Goals
gh stimulation · body composition · fat loss · longevity · cognitive
Cost / mg
Not recorded

How it works

MK-677 (ibutamoren) is an orally active, non-peptide molecule that mimics the hunger hormone ghrelin. It switches on the ghrelin receptor (GHS-R1a) in the pituitary gland and hypothalamus, prompting the body to release more of its own growth hormone (GH), which in turn raises IGF-1. Unlike injected GH, it amplifies the body's natural pulsing pattern of GH release without shutting down the normal feedback system. Because it survives stomach digestion, it can be taken by mouth once daily and keeps GH and IGF-1 elevated for up to about 24 hours. Through the same ghrelin pathway it also increases appetite and can affect sleep, insulin sensitivity, and repair processes.

Overview

Overview

MK-677 (ibutamoren, MK-0677, Nutrobal, L-163,191) is an orally active, non-peptide growth hormone secretagogue and a potent full agonist of the ghrelin receptor (GHS-R1a). It was originally developed by Merck in the 1990s as a candidate treatment for growth hormone deficiency, sarcopenia, and osteoporosis in elderly populations. Patchett and colleagues (1995) described it as the first nonpeptidyl substance with potent, long-lasting oral GH-secretagogue activity in humans, and Howard, Feighner, and colleagues (1996) used it as the pharmacological tool that identified GHS-R1a.

Structurally, MK-677 is a small molecule built on a spiroindoline/spiropiperidine scaffold that survives gastrointestinal degradation, allowing once-daily oral dosing with sustained GH and IGF-1 elevation for up to ~24 hours. GH-releasing activity has also been demonstrated after intravenous, subcutaneous, and intranasal administration.

Mechanism

MK-677 binds GHS-R1a on pituitary somatotrophs and hypothalamic neurons, mimicking endogenous ghrelin. It activates a Gq/11-coupled phospholipase C/IP3/calcium cascade that triggers exocytosis of GH-containing vesicles, and centrally it stimulates GHRH-releasing arcuate neurons while suppressing somatostatin tone (its GH effect is synergistic with GHRH). Importantly, it amplifies natural pulsatile GH secretion — increasing pulse amplitude without changing frequency — and does not suppress the hypothalamic-pituitary axis, leaving negative feedback intact. (One source instead characterizes the net pharmacology as tonic 24-hour activation rather than pulsatile, owing to its half-life plus daily dosing.)

Clinical Evidence

MK-677 has an unusually long clinical research record (>20 years) for a compound in this space:

  • Healthy volunteers under caloric restriction: In a double-blind, placebo-controlled cross-over trial (n=8), 25 mg once daily reversed diet-induced protein catabolism, improving mean nitrogen balance to +0.31 g/day vs -1.48 g/day on placebo. Single-dose peak GH reached 55.9 µg/L (22.6 µg/L after a week) vs ~7-9 µg/L placebo, with IGF-1 and IGFBP-3 increases.
  • GH-deficient adults: 10 mg raised IGF-1 by 52% and 24-h mean GH by 79%; 50 mg raised IGF-1 by 79% and GH by 82%, with the GH response greater in the least-deficient subjects.
  • Elderly adults: GH and IGF-1 rose to young-adult ranges; the pivotal Nass et al. 2008 2-year trial (N=65, 25 mg/day) sustained a 1.5-2x IGF-1 rise without tachyphylaxis and produced a modest fat-free-mass gain (~+1.1 kg).
  • Dose-response (expert estimates): IGF-1 approximately +15-25% at 5 mg, +25-40% at 10 mg, +40-60% at 25 mg, +60-90% at 50 mg.

Key limitation: across RCTs in elderly and hip-fracture patients, large IGF-1 increases (e.g., +84% vs +17% placebo; +51 ng/mL) did not translate into consistent, statistically significant improvements in functional strength or performance. One 24-week trial did show improved gait speed, but most functional endpoints were unchanged. Merck discontinued development after functional endpoints repeatedly failed, and no NDA was submitted.

Additional class-level or early findings include Phase 2 work in muscle wasting, sleep, and bone density; reported height-velocity increases in short children during GHRP treatment; and reduced amyloid deposition and neuronal loss in an Alzheimer's mouse model (5XFAD) — the last two being animal or class-level rather than MK-677-specific controlled findings.

Regulatory Status

MK-677 has not received FDA approval for any indication and remains investigational. It is not legal as a dietary supplement ingredient, is prohibited by WADA, and appears on the DoD Prohibited Dietary Supplement Ingredients List. Despite this, it is widely distributed through gray-market channels as a research chemical and is one of the most prevalent performance-enhancing compounds sold online, marketed for muscle, fat loss, and energy.

What the research shows

155 findings extracted from the 18 sources cited below, strongest evidence first within each group. Every one links to the source it came from.

What human studies found

Based on 26 human trial findings, 19 human study findings, 8 animal findings and 2 expert opinion findings.

  • human trialMK-0677 demonstrated an increase in pulsatile GH secretion for as long as the medications were given for up to 2 years1

  • human trialMK-677 reverses diet-induced protein catabolism2

  • human trialDuring diet and study drug treatment, mean daily nitrogen balance was 0.31 +/- 0.21 g/day in the MK-677 treatment group compared with -1.48 +/- 0.21 g/day in the placebo group2

  • human trialMK-677 improved nitrogen balance integrated over 7 days of treatment with area under curve day 8-14 of +2.69 +/- 5.0 compared to placebo -8.97 +/- 5.26 g.day2

  • human trialStudy involved eight healthy volunteers ages 24-39 years in a double-blind, randomized, placebo-controlled, two-period cross-over design2

  • human trialMK-677 reverses diet-induced protein catabolism2

  • human trialDuring caloric restriction with MK-677 treatment, mean daily nitrogen balance was 0.31 +/- 0.21 g/day compared with -1.48 +/- 0.21 g/day in placebo group2

  • human trialMK-677 improved nitrogen balance integrated over 7 days of treatment with area under curve of +2.69 +/- 5.0 g.day versus -8.97 +/- 5.26 g.day for placebo2

Show 47 more findings

  • human trialIGF-I concentration increased significantly during MK-677 to 264 +/- 31 ng/mL compared with 188 +/- 19 ng/mL with placebo2

  • human trialIGF binding protein-3 increased to 3273 +/- 330 ng/mL with MK-677 treatment compared with 2604 +/- 253 ng/mL placebo2

  • human trialOral administration of MK-677 stimulates the GH/insulin-like growth factor-I (IGF-I) axis in GH-deficient adults5

  • human trialAfter treatment with 10 mg MK-677, IGF-I concentrations increased 52 +/- 20% (65 +/- 6 to 99 +/- 9 micrograms/L)5

  • human trialAfter treatment with 10 mg MK-677, 24 h mean GH concentrations increased 79 +/- 19% (0.14 +/- 0.01 to 0.26 +/- 0.02 microgram/L)5

  • human trialFollowing treatment with 50 mg MK-677, IGF-I concentrations increased 79 +/- 9% (84 +/- 3 to 150 +/- 6 micrograms/L)5

  • human trialFollowing treatment with 50 mg MK-677, 24-h mean GH concentrations increased 82 +/- 29% (0.21 +/- 0.02 to 0.39 +/- 0.04 microgram/L)5

  • human trialSerum IGF binding protein-3 concentrations increased with 10 mg MK-677 (1.2 +/- 0.1 to 1.7 +/- 0.1 micrograms/L)5

  • human trialSerum IGF binding protein-3 concentrations increased with 50 mg MK-677 (1.7 +/- 0.1 to 2.2 +/- 0.2 micrograms/L)5

  • human trialThe GH response to MK-677 was greater in subjects who were the least GH/IGF-I deficient at baseline5

  • human trialMK-0677 at 25mg/day increased mean stair climbing power by 12.5 W at 24-weeks in elderly hip fracture patients7

  • human trialGait speed increased by 0.7-score difference in MK-0677 treated patients compared to placebo (p = 0.011)7

  • human trialMK-0677 group experienced fewer falls during the study compared to placebo7

  • human trialIncrease in plasma IGF-1 levels was not paralleled by improvement in most functional performance measures7

  • human trialMK-0677 treatment increased serum IGF-I levels by 84% compared with an increase of 17% on placebo8

  • human trialThere were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score8

  • human trialMK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, but these differences were not statistically significant8

  • human trialMK-0677 treatment increased serum IGF-I but uncertainty exists regarding clinically significant effects on physical function8

  • human studyGHSs might improve growth velocity in children6

  • human studyGHSs stimulate appetite6

  • human studyGHSs improve lean mass in wasting states and in obese individuals6

  • human studyGHSs decrease bone turnover6

  • human studyGHSs increase fat-free mass6

  • human studyGHSs improve sleep6

  • human studyThe GH-releasing activity of GHRPs including MK-0677 is marked and dose-related9

  • human studyProlonged administration of GHRPs increases IGF-1 levels in both animals and humans9

  • human studyThe GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations, increasing from birth to puberty, persisting in adulthood, and decreasing thereafter9

  • human studyBy the sixth decade of life, the activity of GHRPs is reduced but still marked and higher than GHRH9

  • human studyGHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as acromegaly, anorexia nervosa and hyperthyroidism9

  • human studyReduced GH responses after GHRP administration have been reported in idiopathic GH deficiency, idiopathic short stature, obesity and hypothyroidism9

  • human studyIn patients with pituitary stalk disconnection or Cushing's syndrome, somatotrope responsiveness to GHRPs is almost absent9

  • human studyMK-677 co-administered with LGD-4033 increased body mass by 6.0%13

  • human studyMK-677 co-administered with LGD-4033 increased total lean body mass by 3.1%13

  • human studyMK-677 co-administered with LGD-4033 increased trunk lean body mass by 6.6%13

  • human studyMK-677 co-administered with LGD-4033 increased appendicular lean body mass by 4.3%13

  • human studyMK-677 co-administered with LGD-4033 increased total fat mass by 15.4%13

  • human studyMost measured variables returned to pre-cycle values post-cycle except total fat mass, appendicular fat mass, bone area, total cholesterol and low-density lipoprotein-cholesterol13

  • animalMK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers14

  • animalFollowing initial oral administration of MK-0677, GH secretion was increased 7.9- to 9.8-fold at 1.0 mg/kg, 5.6-fold at 0.5 mg/kg, or 3.9-fold at 0.25 mg/kg16

  • animalWith repeat MK-0677 administration, the GH response was decreased by 41-77%16

  • animalSerum IGF-I levels were significantly increased over control levels at all dosage levels by 480 min on the first day of MK-0677 administration16

  • animalWith repeated administration, IGF-I levels were increased up to 126% and remained elevated through 14 days16

  • animalMK-0677 stimulated increases in cortisol secretion on the first day of treatment16

  • animalA decreased cortisol response was observed following repeated daily treatment with MK-067716

  • animalChronic oral administration of MK-0677 was associated with significant increases in GH and IGF-I levels that were maintained for the duration of the treatment16

  • expert opinionFew long-term, rigorously controlled studies have examined the efficacy and safety of GHSs6

  • expert opinionGHS can significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy18

How it works

Based on 5 human trial findings, 3 human study findings, 13 animal findings, 4 in vitro findings and 7 expert opinion findings.

  • human trialMK-677 is an orally active nonpeptide mimic of GH-releasing peptide2

  • human trialMK-677 is an orally active nonpeptide mimic of GH-releasing peptide2

  • human trialMK-677 is a GH releasing peptide (GHRP)-mimetic5

  • human trialIGF-1 levels in MK-0677 treated patients increased by 51.4 ng/ml compared to placebo (p < 0.001)7

  • human trialMK-0677 is an orally active growth hormone secretagogue8

  • human studyIbutamoren is incorporated into human hair3

  • human studyGHSs promote pulsatile release of GH that is subject to negative feedback and can prevent supra-therapeutic levels of GH6

  • human studyThe GH-releasing activity of GHRPs is synergistic with GHRH9

Show 24 more findings

  • animalGhrelin improves cognitive impairments and attenuates neuronal death and neuroinflammation in several neurological disorders14

  • animalMK-0677 inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice14

  • animalActivation of the ghrelin receptor with MK-0677 inhibited the Aβ burden, neuroinflammation, and neurodegeneration14

  • animalIn conscious male rats, both central and systemic injection of MK-0677 induced fos-like immunoreactivity specifically within the arcuate nucleus indicating selective neuronal activation15

  • animalMK-0677 induced-activation was generally confined close to the wall of the third ventricle15

  • animalIntravenous injection of MK-0677 in urethane anaesthetized rats increased the electrical activity of a population of antidromically identified neuroendocrine arcuate neurons15

  • animalThe activity of neuroendocrine arcuate neurons excited by MK-0677 injection could be attenuated by a subsequent systemic injection of somatostatin15

  • animalSystemic and central administration of MK-0677 activates a population of neurons in the arcuate nucleus15

  • animalMK-0677 is a novel, orally active GH secretagogue that stimulates an immediate and long-lasting increase in serum GH levels in dogs16

  • animalSignificant elevations in IGF-I levels were associated with the increased GH secretion16

  • animalCortisol secretion was also increased following MK-0677 administration16

  • animalCirculating IGF-I concentrations regulate GH and cortisol response to MK-067716

  • animalIGF-I mediated negative feedback on both the GH and cortisol axes16

  • in vitroMK-0677 (ibutamoren) is an orally active non-peptide growth hormone secretagogue that binds to the ghrelin receptor stimulating the secretion of endogenous growth hormone10

  • in vitroMK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor14

  • in vitroMK-0677 is a nonpeptidyl growth hormone secretagogue15

  • in vitroMK-0677 has been shown to directly stimulate growth hormone release from isolated pituitary cells15

  • expert opinionMK-677 is a growth hormone secretagogue4

  • expert opinionMK-0677 is a non-peptidyl GHRP mimetic that acts via GHRP receptors and is considered the most interesting molecule among non-peptidyl GHRPs9

  • expert opinionIbutamoren (MK-0677) is a potent, long-acting, selective non-peptide growth hormone secretagogue that can be taken orally11

  • expert opinionIbutamoren mesylate, or MK-0677, is an orally active, nonpeptide growth hormone secretagogue that has been developed to stimulate excretion of endogenous growth hormone12

  • expert opinionMK-677 is a growth hormone secretagogue13

  • expert opinionMK-677, also known as Ibutamoren, is a "growth hormone secretagogue," a substance that stimulates the production of growth hormone.17

  • expert opinionGHS including sermorelin, GHRP-2, GHRP-6, ibutamoren, and ipamorelin are potent GH and IGF-1 stimulators18

Dosing

Based on 1 human trial finding and 1 animal finding.

  • human trialMK-677 administered orally at 10 or 50 mg once daily5

  • animalDaily MK-0677 administration increased IGF-I levels over 24 h, but alternate day MK-0677 administration did not show such sustained increase16

How the body handles it

Based on 5 human trial findings, 4 human study findings, 12 animal findings and 1 in vitro finding.

  • human trialMK-677 produced a peak GH response of 55.9 +/- 31.7 micrograms/L after single dose and 22.6 +/- 9.3 micrograms/L after a week of dosing2

  • human trialMean IGF-I concentration increased significantly during MK-677 to 264 +/- 31 ng/mL compared with 188 +/- 19 ng/mL with placebo2

  • human trialMean IGF binding protein-3 for the last 5 days of MK-677 treatment was significantly increased to 3273 +/- 330 ng/mL compared with placebo 2604 +/- 253 ng/mL2

  • human trialNo significant difference in IGF binding protein-2 was found between MK-677 and placebo treatments2

  • human trialMK-677 produced peak GH response of 55.9 +/- 31.7 micrograms/L after single dose and 22.6 +/- 9.3 micrograms/L after one week of dosing2

  • human studyA single 10 mg dose of ibutamoren (MK-677) administered to a male volunteer resulted in hair concentration of 1.3 pg/mg in the 0 to 1 cm segment 4 weeks after exposure3

  • human studyAfter consumption of 60 capsules of 10 mg ibutamoren over 90 days, hair concentration reached 224 pg/mg in the 0 to 4 cm segment 4 weeks after drug discontinuation3

  • human studyibutamoren mesylate is an orally available small-molecule GH secretagogue6

Show 14 more findings

  • human studyMK-0677 demonstrates GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration9

  • animalMK-0677 and its O-dealkylated metabolite can be extracted from equine hair and analysed by liquid chromatography tandem mass spectrometry10

  • animalMK-0677 can be detected in all hair samples collected following oral administration to a Thoroughbred racehorse, up to 209 days in mane and 358 days in tail10

  • animalInternal incorporation of MK-0677 via bloodstream was indicated for hair samples collected at later time points (≥52 days)10

  • animalA combination of internal incorporation and external deposition was indicated for hair samples collected at the earlier time point (2 days)10

  • animal22 metabolites of ibutamoren were identified (17 phase I and 5 phase II)11

  • animalOxidation of ibutamoren leads to hydroxylated metabolites (mono and di)11

  • animalThe study detected dissociated side chains (benzyl group and 2-amino-2-methylpropanamide) and hydrogenated metabolites11

  • animalGlucuronic acid conjugated analogs of ibutamoren were detected during phase II of the study, but no sulfonic acid conjugated analogs were observed11

  • animalThe major metabolites can be detected up to 96 hours after a single dose, and ibutamoren can persist for up to 72 hours11

  • animal13 metabolites were subsequently detected in urine and nine in plasma collected post-administration, alongside the parent compound in both matrices12

  • animalThe longest duration of detection was observed for an O-dealkylated metabolite of MK-067712

  • animalMK-0677 and the O-dealkylated metabolite were found to be excreted largely unconjugated in urine and plasma12

  • in vitroFourteen phase I metabolites were identified in vitro12

Safety and side effects

Based on 8 human trial findings, 21 human study findings and 1 expert opinion finding.

  • human trialNeither serum cortisol nor PRL response was significantly greater after 7 days of MK-677 dosing compared with placebo2

  • human trialMK-677 (25 mg) was generally well tolerated and without clinically significant adverse experiences2

  • human trialMK-677 25 mg was generally well tolerated and without clinically significant adverse experiences2

  • human trialNo significant difference in serum cortisol or prolactin response after 7 days of MK-677 dosing compared with placebo2

  • human trialThe drug was generally well tolerated, with no significant changes from baseline in circulating concentrations of cortisol, PRL, and thyroid hormones5

  • human trialFasting and postprandial insulin and postprandial glucose increased significantly after MK-677 treatment5

  • human trialTrial was terminated early due to a safety signal of congestive heart failure in a limited number of patients7

  • human trialMK-0677 has an unfavorable safety profile in elderly hip fracture patients7

Show 22 more findings

  • human studyThe minimal detectable dose of ibutamoren in hair has been established through this study3

  • human studySide effects of MK-677 include oedema, increased appetite and muscle pain4

  • human studyReports of hepatotoxicity from MK-677 are scarce4

  • human studyMK-677 consumption for 2 months can cause transaminitis in otherwise healthy individuals4

  • human studyLiver function tests returned to normal limits after stopping MK-677 supplement4

  • human studyGHSs are well tolerated6

  • human studyThere is concern for increases in blood glucose because of decreases in insulin sensitivity with GHS use6

  • human studyGHRPs undergo partial desensitization during continuous infusion, less during intermittent administration9

  • human studyMK-677 co-administered with LGD-4033 negatively impacted bone mineral content, decreasing by 3.60%13

  • human studyMK-677 co-administered with LGD-4033 negatively impacted bone area, decreasing by 1.1%13

  • human studyMK-677 co-administered with LGD-4033 negatively impacted bone mineral density, decreasing by 2.1%13

  • human studyMK-677 co-administered with LGD-4033 increased serum cholesterol by 14.8%13

  • human studyMK-677 co-administered with LGD-4033 increased triglycerides by 39.2%13

  • human studyMK-677 co-administered with LGD-4033 increased low-density lipoprotein-cholesterol by 40.0%13

  • human studyMK-677 co-administered with LGD-4033 decreased high-density lipoprotein-cholesterol by 36.4%13

  • human studyMK-677 co-administered with LGD-4033 increased aspartate aminotransferase by 95.8%13

  • human studyMK-677 co-administered with LGD-4033 increased alanine aminotransferase by 205.0%13

  • human studyMK-677 co-administered with LGD-4033 decreased free testosterone by 85.7%13

  • human studyMK-677 co-administered with LGD-4033 decreased total testosterone by 62.3%13

  • human studyMK-677 co-administered with LGD-4033 decreased sex hormone-binding globulin by 79.6%13

  • human studyFollicle-stimulating hormone was below clinical reference values at 1.2 IU/L on-cycle and 1.3 IU/L post-cycle following MK-677 and LGD-4033 co-administration13

  • expert opinionA number of health risks have been associated with the use of MK-677 (Ibutamoren).17

What people use it for

Based on 1 human study finding, 1 animal finding, 7 expert opinion findings and 1 anecdotal finding.

  • human studyAn increase in height velocity has been reported in short children during chronic GHRP treatment9

  • animalMK-0677 might have potential as a treatment of the early phase of AD14

  • expert opinionMK-0677 is one of the most prevalent performance-enhancing compounds currently available online10

  • expert opinionMK-0677 has been evaluated for the treatment of a range of clinical conditions but is not available therapeutically12

  • expert opinionIt is not approved for human use, which makes it an unapproved drug.17

  • expert opinionIt is also not legal for use as an ingredient in dietary supplements or any other consumer or commercial products.17

  • expert opinionIt can only be used for research purposes.17

  • expert opinionMK-677 is on the DoD Prohibited Dietary Supplement Ingredients List and the World Anti-Doping Agency Prohibited List.17

Show 2 more findings

  • expert opinionGrowth hormone secretagogues (GHS) have emerged as a potential novel adjunctive therapy for some of the symptoms of hypogonadism18

  • anecdotalMK-677 is currently marketed with claims to help build muscle or increase muscle mass, decrease body fat, and increase energy.17

Other findings

Based on 2 human study findings and 2 expert opinion findings.

  • human studyLinearity for ibutamoren hair detection was verified from 0.5 to 250 pg/mg3

  • human studyThe limit of detection for ibutamoren in hair was 0.1 pg/mg3

  • expert opinionMK-0677 is widely available to purchase online, sold as 'supplement' products12

  • expert opinionCurrent data on clinical efficacy of GHS largely remain lacking18

Points of contention

Where the evidence is unsettled, thin, or says less than the popular claim — worth knowing before you draw conclusions.

Contested

Whether MK-677 raises cortisol is not consistent across sources.

Human RCTs report no significant cortisol or prolactin elevation at standard doses (MK-677, an orally active growth hormone secretagogue, reverses ..., Oral Administration of Growth Hormone (GH) Releasing Peptide-Mimetic MK-677 Stimulates the GH/Insulin-Like Growth Factor-I Axis in Selected GH-Deficient Adults 1, MK-677 Ibutamoren UK 2026 Research Reference - Peptides Lab UK, MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism - PubMed), whereas a dog study found MK-0677 increased cortisol on the first day of treatment (attenuated with repeat dosing) (Repeat administration of the GH secretagogue MK-0677 increases and maintains elevated IGF-I levels in beagles.).

Contested

Sources disagree on whether MK-677 preserves the body's natural pulsatile GH release or instead drives sustained, tonic stimulation.

Most references state that MK-677 amplifies GH pulse amplitude while leaving pulse frequency unchanged, thereby preserving the physiological pulsatile secretion pattern (MK-677 (Ibutamoren): Research Evidence & Safety Profile | PeptideInsight; MK-677: 42 Studies Reviewed | PepCodex; MK-677: History, Development, and Mechanism of Action | HealthRX.com; MK-677 Guide: Ibutamoren Benefits, Evidence & Risks | PeptideMark; MK-677 (Ibutamoren) Research Guide at Path to Peptides). One reference directly contradicts this: the MK-677 Ibutamoren UK 2026 Research Reference (Peptides Lab UK) states that its 4-6 hour half-life combined with once-daily dosing keeps trough concentrations pharmacologically active, so it 'produces tonic rather than pulsatile receptor activation' and, in its own words, 'does not preserve physiological GH pulsatility.' The disagreement is therefore not one of emphasis but about whether pulsatility is retained at all.

Limited evidence

IGF-1 rises reliably but functional benefits were not demonstrated.

Multiple RCTs in elderly/hip-fracture patients confirmed large IGF-1 increases but failed to show statistically significant improvements in most functional performance measures (MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study., The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture., Superpower), and Merck discontinued development after functional endpoints failed. A review notes few long-term, rigorously controlled efficacy/safety studies exist for GHS.

Limited evidence

Cardiac safety concern based on a terminated trial in a specific frail population.

The congestive heart failure signal that led to early termination arose in an elderly hip-fracture trial; whether it generalizes to other populations is not established, and the number of affected patients was limited (MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.). Sources describe it as leaving 'lingering questions' rather than a definitive causal finding.

Single source

Severe adverse endocrine/lipid/liver changes come from a single combination-use case study.

The dramatic decreases in testosterone/SHBG, large LDL and triglyceride increases, and ~2-3x liver enzyme elevations are from one human observational study of MK-677 combined with the SARM LGD-4033 (LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.), so these effects cannot be attributed to MK-677 alone.

Single source

Some pharmacokinetic and sleep specifics rest on single, lower-tier sources.

The 'up to 50% increase in REM and Stage 4 deep sleep' figure and ~60-65% bioavailability appear in a single tier-3 source (MK-677: 42 Studies Reviewed (2026) | PepCodex); detailed PK parameters (CYP3A4 metabolism, Tmax, high-fat meal effect, dose-response IGF-1 percentages) come largely from one tier-3 source (MK-677 Ibutamoren UK 2026 Research Reference - Peptides Lab UK).

Limited evidence

Neuroprotective and growth-velocity uses are early/animal or class-level only.

The Alzheimer's-model benefit is from mice (MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.), and reported height-velocity increases in children and other therapeutic uses are from GHRP-class observations rather than MK-677-specific controlled trials (Growth hormone-releasing peptides., The Safety and Efficacy of Growth Hormone Secretagogues.).

Inconsistency

Two sources give wildly different single-dose durations — roughly 24 hours versus 6-14 days.

Reference guides disagree by more than an order of magnitude on how long a single dose of MK-677 keeps GH and IGF-1 elevated. The PtP Wiki research guide (MK-677 (Ibutamoren): Research Guide | PtP Wiki) states effects last 'up to 24 hours from a single daily dose,' with a plasma half-life of ~4-6 hours and a pharmacodynamic duration of ~24 hours that is used to justify once-daily dosing. The PeptideMark guide (MK-677 Guide: Ibutamoren Benefits, Evidence & Risks (2026) | PeptideMark) instead states that clinical effects last '6-14 days after a single dose.' A multi-day effect is hard to reconcile with the ~4-6 hour plasma half-life and the once-daily-dosing rationale both described by the PtP Wiki source, so the 6-14 day figure should be treated with caution.

What you may have heard

The injectable and intranasal routes listed for MK-677 come from a review of the whole GH-releasing peptide family, not from data on MK-677 itself, which the literature describes as an orally active molecule.

The review Growth hormone-releasing peptides attributes marked, dose-related GH-releasing activity "after intravenous, subcutaneous, intranasal and even oral administration" to GH-releasing peptides as a class; MK-0677 is named within it only as the most interesting non-peptidyl member of that class, not as the specific compound tested by each route. Across compound-specific references MK-677 is consistently characterized as a non-peptide, orally active molecule engineered for oral bioavailability, with oral listed as its studied route and injection reserved for the peptide secretagogues it was designed to replace. Presenting the class-level routes as established MK-677 routes overstates how the compound is actually characterized and used.

What you may have heard

The exact receptor-binding figure and the "no activity anywhere else" selectivity profile each rest on a single source, and the two sources describe the compound's potency in different terms.

The specific ghrelin-receptor binding affinity of 6.5 nM is reported only in MK-677: Mechanism, Dosing & Evidence (Pepteligence), which also notes that nonpeptide secretagogues like MK-677 can behave both as simple agonists and as positive or negative allosteric modulators at the same receptor. The detailed selectivity panel — full agonism at GHSR-1a with minimal activity at motilin and neuromedin U receptors and no significant activity at GHRH, somatostatin, or monoamine receptors — appears only in the commercial vendor reference MK-677 Ibutamoren UK 2026 Research Reference (Peptides Lab UK), which expresses potency not as a binding affinity but as an "EC50 in the low nanomolar range." Neither the precise affinity value nor the selectivity panel is independently corroborated between the two references.

Other

Second-hand summaries of the pivotal Nass et al. 2008 trial disagree on how long it ran and how much IGF-1 rose.

The description of the pivotal Nass et al. 2008 trial rests on secondary summaries that do not agree on its basic parameters. "MK-677 (Ibutamoren): Oral GH Secretagogue (2026)" describes it as a 12-month randomized trial of 25 mg daily versus placebo in elderly subjects, with IGF-1 rising 1.5-2x baseline and sustained without tachyphylaxis. "MK-677 (Ibutamoren): History, Development, and Mechanism of Action | HealthRX.com" instead describes a 2-year trial in 65 healthy elderly adults, with IGF-1 rising roughly 40-60% above baseline. The review "Growth Hormone Secretagogues as Potential Therapeutic Agents" notes that MK-0677 sustained pulsatile GH secretion for up to 2 years but does not attach that duration to the Nass trial. None of these is the primary trial publication, and the duration and IGF-1 figures differ between them.

Contested

The two sources disagree on how much IGF-1 rises at the standard 25 mg/day dose.

peptideslabuk.com (MK-677 Ibutamoren UK 2026 Research Reference - Peptides Lab UK) reports a dose-response of IGF-1 +40-60% above baseline at 25 mg/day (and +60-90% at 50 mg). thepeptidetoolkit.com (MK-677 (Ibutamoren): Oral GH Secretagogue (2026)) instead reports IGF-1 rising to 1.5-2x baseline at 25 mg/day, i.e. a +50-100% increase, citing the Nass 2008 12-month trial. These two 25 mg figures overlap only partially and the toolkit's upper end (100%) exceeds the lab reference's 25 mg range entirely, so they cannot both be stated as the single value for that dose.

Using it with other compounds

Check a stack
  • TesamorelinSame downstream effect

    Worth caution

    Tesamorelin is a stabilized GHRH analog that raises GH/IGF-1 through the GHRH receptor, distinct from MK-677's ghrelin-receptor pathway. Both feed the same GH/IGF-1 axis, so they can be additive on GH output. Note a practical tension: tesamorelin is used specifically to reduce visceral fat, whereas MK-677 raises appetite and can promote fluid retention and insulin resistance, which may partly counter the body-composition goal.

    Tier 3Largely anecdotal — commonly discussed

    Timing Monitor fasting glucose/insulin, since both GH-raising agents plus MK-677's appetite drive can worsen insulin sensitivity.

    Shares GH axis · IGF1 signaling · lipolysis

  • TirzepatideStack with caution

    Worth caution

    MK-677 is a ghrelin-receptor agonist that increases hunger and can raise blood glucose and reduce insulin sensitivity — directly opposing tirzepatide's appetite suppression and glucose-lowering effects. Stacking them works at cross-purposes on both appetite and glycemic control, so their metabolic goals partly cancel out.

    Tier 4Theoretical — not established
    What the research doesn't establish
    The claim that MK-677 opposes tirzepatide's glucose-lowering and insulin-sensitizing effects is not established here: MK-677's documented actions are limited to GH/IGF-1 axis activation, increased appetite, and lean mass gain, with no shown effect on blood glucose or insulin sensitivity. Any glycemic opposition between the two therefore rests on tirzepatide's effects alone.
  • SemaglutideStack with caution

    Worth caution

    MK-677 increases appetite while semaglutide suppresses it — opposing effects on food intake. Some use GLP-1 agonists deliberately to offset MK-677's hunger, but the two also pull insulin sensitivity in different directions (MK-677 can raise glucose/reduce insulin sensitivity; semaglutide improves glycemic control), so glucose should be monitored.

    Tier 4Theoretical — not established
    What the research doesn't establish
    MK-677 (via GHS-R1a) and semaglutide (via the GLP-1 receptor) act on separate receptors and pathways, so their appetite and glucose effects are inferred to oppose one another rather than being demonstrated to interact when the two are taken together. No study establishes how combined use affects glycemic control or net food intake in the same person.
  • SermorelinSame downstream effect

    May be complementary

    Sermorelin is a GHRH-receptor agonist, a different upstream trigger from MK-677's ghrelin-receptor action, yet both raise pulsatile GH and IGF-1 and both are reported to deepen slow-wave sleep. Using a GHRH signal plus a ghrelin-mimetic can enhance the GH pulse more than either alone, and their overlapping sleep benefits reinforce each other.

    Tier 3Largely anecdotal — commonly discussed

    Timing Both are commonly dosed at night to work with the natural GH pulse and sleep architecture; keep IGF-1 in a physiological range.

    Shares GH axis · IGF1 signaling · protein synthesis · sleep architecture

  • HexarelinSame mechanism

    Worth caution

    MK-677 is an oral ghrelin-mimetic that hits the same GHS-R1a receptor hexarelin does. Combining them is redundant — both compete for and desensitize the same receptor — and MK-677's long half-life keeps that receptor occupied around the clock, which can blunt the pulse a short-acting injectable like hexarelin is trying to create. Pick one GHS-R1a agonist rather than layering two.

    Tier 2Supported by animal / early studies

    Shares GH axis · IGF1 signaling

  • IpamorelinSame mechanism

    Worth caution

    MK-677 (ibutamoren) is an oral non-peptide that hits the same ghrelin receptor (GHS-R1a) as ipamorelin. Running both means competing for the identical receptor and GH-release pathway, so the effect is redundant rather than additive. MK-677 also produces a long, sustained receptor activation plus notable appetite stimulation and water retention — layering ipamorelin on top adds little extra GH while compounding those side effects. Most people should use one GHS-R1a agonist, not two.

    Tier 3Largely anecdotal — commonly discussed

    Timing Pick one ghrelin-receptor agonist rather than stacking; MK-677's long half-life keeps the receptor occupied for many hours.

    Shares GH axis · IGF1 signaling

  • DSIPComplementary

    May be complementary

    Both are used to improve sleep quality but through completely different routes: DSIP deepens slow-wave (delta) sleep via GABA-A enhancement and opioid/enkephalin signaling, while MK-677 raises GH/IGF-1 and has been reported to increase REM and deep sleep. Stacking them targets sleep architecture from two angles, which can be additive. Note that MK-677 also raises appetite and can cause vivid dreams or morning grogginess in some users, so evaluate how the combination affects your own sleep.

    Tier 4Theoretical — not established

    Timing Both are typically taken in the evening/before bed to align with the natural nighttime GH pulse and sleep onset.

    Shares sleep architecture

  • Follistatin-344Complementary

    May be complementary

    MK-677 elevates GH/IGF-1 and improves nitrogen balance, supporting protein synthesis from the anabolic-hormone side, while Follistatin releases the myostatin brake. The two attack muscle growth from separate angles, making them additive rather than redundant.

    Tier 4Theoretical — not established

    Shares protein synthesis · IGF1 signaling

  • KlothoStack with caution

    Worth caution

    A key part of Klotho's longevity/anti-senescence profile is that it dampens IGF-1/insulin intracellular signaling. MK-677 does the opposite — it strongly and continuously raises circulating IGF-1 (and IGFBP-3). If someone is using Klotho specifically for anti-aging benefit, a sustained IGF-1 elevation from MK-677 works against that mechanism, so the goals partly conflict and this pairing is worth understanding rather than assuming synergy.

    Tier 4Theoretical — not established

    Shares IGF1 signaling

  • AOD-9604Stack with caution

    Worth caution

    MK-677 raises GH/IGF-1 (which can support lipolysis) but also markedly stimulates appetite and can promote fluid retention, potentially working against AOD-9604's fat-loss goal. Worth understanding the appetite trade-off before combining.

    Tier 4Theoretical — not established
  • CJC-1295Complementary

    Worth caution

    MK-677 is an oral ghrelin-receptor agonist that raises GH/IGF-1 via a different receptor than CJC-1295. The mechanisms are complementary (pulse amplitude from GHRH vs. secretagogue-driven pulses), but because MK-677 produces sustained IGF-1 elevation, combining the two can push IGF-1 high — monitor levels and watch for water retention/appetite effects.

    Tier 3Largely anecdotal — commonly discussed

    Timing MK-677 is long-acting/daily; monitor IGF-1 if combined with a GHRH analog.

    Shares GH axis · protein synthesis · IGF1 signaling

  • CagrilintideStack with caution

    Worth caution

    MK-677 is a ghrelin-receptor agonist that reliably INCREASES appetite, which directly opposes cagrilintide's core action of suppressing appetite and increasing satiety. Running them together works against your weight-management goal and can blunt cagrilintide's benefit.

    Tier 4Theoretical — not established

    Shares appetite regulation

Safety and side effects

Safety & Side Effects

In short-term healthy-volunteer and GH-deficient RCTs, MK-677 was generally well tolerated, with no significant increase in cortisol, prolactin, or thyroid hormones at standard doses. Growth hormone secretagogues as a class are described as generally well tolerated, with the principal concern being glucose/insulin effects.

Commonly reported effects

  • Increased appetite (via the ghrelin pathway)
  • Fluid retention / edema
  • Muscle pain
  • Modest fasting glucose elevation (HbA1c ~+0.3%) and reduced insulin sensitivity — some sources state MK-677 consistently worsens insulin sensitivity and raises fasting glucose, particularly at higher doses

Dose considerations

Higher doses (50 mg, 100 mg) showed diminishing IGF-1 returns and proportionally larger side effects in early Merck trials.

Cardiac signal

A congestive heart failure safety signal emerged in an elderly hip-fracture trial, prompting its early termination and leading to the conclusion that MK-0677 had an unfavorable safety profile in that frail population. This arose in a specific, frail patient group with a limited number of affected patients; sources describe it as leaving lingering questions about cardiac safety rather than a definitive causal finding, and it is not established whether it generalizes to other populations.

Liver and endocrine reports

  • Hepatotoxicity (transaminitis): Consumption for ~2 months has been reported to cause elevated liver enzymes in otherwise healthy individuals, with normalization after stopping; such reports are described as scarce.
  • Case reports document hepatotoxicity, gynecomastia, hypogonadotropic hypogonadism, and dyslipidemia, particularly when combined with SARMs.
  • In a single human observational combination study, MK-677 15 mg with the SARM LGD-4033 10 mg for 5 weeks produced dramatic changes: total fat mass +15.4%, LDL +40.0%, triglycerides +39.2%, HDL -36.4%, ALT +205%, AST +95.8%, and total/free testosterone -62.3%/-85.7%. These effects cannot be attributed to MK-677 alone — they reflect combination use, and most (except fat mass, bone area, and cholesterol/LDL) reverted after cessation.

Notes on contested findings

While human RCTs report no significant cortisol elevation at standard doses, a dog study found MK-0677 raised cortisol on the first day of dosing (attenuated with repeated dosing). The '~50% increase in REM and Stage 4 deep sleep' figure rests on a single lower-tier source.

MK-677 is investigational and not approved for human use. It is prohibited by WADA and is not a legal dietary supplement ingredient. This section reports what the research describes, not guidance to use the compound.

Reconstitution and handling

Preparation & Dosing

No dose has been established for this compound. No regulatory label exists for it, so the figures below are what sources report — not guidance.

Unlike injectable peptides, MK-677 is an orally active, non-peptide small molecule and does not require reconstitution with bacteriostatic water. It is resistant to gastrointestinal degradation and is typically administered by mouth, most commonly as a capsule or oral liquid in gray-market products. GH-releasing activity has also been demonstrated after intravenous, subcutaneous, and intranasal administration in research settings.

Pharmacokinetics

  • Oral bioavailability: ~60-65% (single lower-tier source)
  • Tmax: 1-2 hours
  • Steady state: reached after 5-7 days of once-daily dosing
  • Metabolism: primarily hepatic via CYP3A4
  • Half-life: reported as ~4-6 hours (plasma) with a ~24-hour biological effect on the GH/IGF-1 axis in some sources, and ~24 hours in others
  • Food effect: a high-fat meal delays Tmax by ~1 hour and reduces Cmax ~20% but does not change total AUC

A single dose sustains GH and IGF-1 elevation for up to ~24 hours, consistent with the 4-6 hour plasma half-life and the basis for once-daily dosing; after stopping, IGF-1 typically normalizes over roughly 4-7 days. (One lower-tier vendor source claims effects on GH/IGF-1 last 6-14 days after a single dose, but this is not supported by the compound's pharmacokinetics and contradicts the once-daily-dosing rationale.) MK-677 is incorporated into hair and detectable there for at least 4 weeks after a single dose (useful for anti-doping detection).

Dosing as studied and reported

  • Validated clinical trial dose: 25 mg once daily orally (used across the healthy-volunteer, elderly, and Nass et al. trials).
  • Community/anecdotal use: typically 10-25 mg, with 25 mg a common ceiling and 10 mg a conservative starter; reported cycle lengths range from 8 weeks to 2 years.
  • Diminishing returns: 50 mg and 100 mg doses showed smaller incremental IGF-1 gains with disproportionately larger side effects.
  • Dosing frequency (animal data): in dogs, daily administration sustained IGF-1 increases over 24 h, whereas alternate-day dosing did not.

These figures describe doses used in research and reported in the community; they are not a recommendation. MK-677 is investigational, unapproved for human use, and prohibited by WADA.

Sources

Ordered by evidence quality — the strongest first.

  1. Growth Hormone Secretagogues as Potential Therapeutic Agents to ...(opens in a new tab)
    Tier 1Web · academic.oup.com
  2. MK-677, an orally active growth hormone secretagogue, reverses ...(opens in a new tab)
    Tier 1Web · pubmed.ncbi.nlm.nih.gov
  3. Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2026
  4. Hepatotoxicity induced by MK-677.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2025
  5. Oral Administration of Growth Hormone (GH) Releasing Peptide-Mimetic MK-677 Stimulates the GH/Insulin-Like Growth Factor-I Axis in Selected GH-Deficient Adults 1(opens in a new tab)
    Tier 1Web · researchgate.net · 2024
  6. The Safety and Efficacy of Growth Hormone Secretagogues.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  7. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2011
  8. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 2004
  9. Growth hormone-releasing peptides.(opens in a new tab)
    Tier 1PubMed · pubmed.ncbi.nlm.nih.gov · 1997
  10. Detection of the growth hormone secretagogue MK-0677 in equine hair following oral administration.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2023
  11. Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping control.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  12. Equine metabolism of the growth hormone secretagogue MK-0677 in vitro and in urine and plasma following oral administration.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  13. LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2022
  14. MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 2018
  15. The nonpeptide growth hormone secretagogue, MK-0677, activates hypothalamic arcuate nucleus neurons in vivo.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1998
  16. Repeat administration of the GH secretagogue MK-0677 increases and maintains elevated IGF-I levels in beagles.(opens in a new tab)
    Tier 2PubMed · pubmed.ncbi.nlm.nih.gov · 1997
  17. Performance Enhancing Substance: MK-677 (Ibutamoren)(opens in a new tab)
    Tier 3Web · opss.org
  18. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males.(opens in a new tab)
    Tier 3PubMed · pubmed.ncbi.nlm.nih.gov · 2020

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