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MK-677

An orally active growth hormone secretagogue that mimics ghrelin to stimulate GH and IGF-1 release.

BModerateModerate Data
Last updated 27 citations
TL;DR

MK-677 is a once-daily pill that tricks the ghrelin receptor — the hunger receptor — into telling your pituitary to release growth hormone. It is not a peptide and not a SARM; it is a conventional small-molecule drug. It reliably raises IGF-1 by 40–90%, deepens sleep, and adds a kilogram or two of lean mass, all of which Merck demonstrated in real trials. What it also does, just as reliably, is make you hungry and push your blood sugar and insulin in the wrong direction, which is the main reason Merck never got it approved for anything and why FDA keeps it on its riskier-compounding list.

What is MK-677?

MK-677 (Ibutamoren) is a non-peptide, orally active growth hormone secretagogue. While technically not a peptide, it is commonly discussed alongside peptides because it acts on the same ghrelin receptor (GHS-R1a) as peptide secretagogues like Ipamorelin. Its oral bioavailability makes it unique in the GH-optimization space.

What MK-677 Is Investigated For

MK-677 (ibutamoren) is a non-peptide, orally active ghrelin receptor agonist investigated for GH/IGF-1 elevation, body composition improvement, sleep quality, and muscle preservation — its oral bioavailability being its main practical differentiator from injectable peptide secretagogues like ipamorelin. The strongest evidence comes from Merck's substantial 1990s–2000s clinical program: the 2008 Nass 2-year RCT (n=65, healthy older adults) established sustained IGF-1 elevation and a 1.6 kg fat-free-mass advantage over placebo, and multiple shorter trials showed 40–90% IGF-1 elevation, increased REM and stage IV sleep, and ghrelin-mediated appetite increase. The honest caveats are substantial: Merck's program never produced an approved indication (Alzheimer's trial failed, a Phase IIb hip-fracture trial was terminated early because of a congestive heart failure safety signal, and functional-performance benefits in elderly populations did not meet the regulatory bar despite body-composition changes). Glucose tolerance and insulin sensitivity reliably worsen with sustained use — this is the clearest duration-related safety signal. MK-677 is not FDA-approved, it is not a peptide (it is a small-molecule spiropiperidine metabolized by CYP3A4 with the associated drug-interaction profile), and the 'SARM' and 'oral HGH' framings common in research-chemical marketing are both wrong.

Oral GH secretagogue (no injection needed)
Moderate70%
Increased IGF-1 levels
Strong90%
Improved sleep quality
Emerging50%
Muscle preservation
Emerging50%

History & Discovery

MK-677 (ibutamoren, also coded MK-0677) was discovered and developed by Merck Research Laboratories in the mid-1990s, emerging from a medicinal-chemistry program aimed at finding orally bioavailable mimetics of the peptide GH secretagogues (GHRP-6, GHRP-2) that had previously demonstrated potent GH release but required injection. Merck chemists identified a non-peptide spiropiperidine scaffold that retained high-affinity agonism at the ghrelin receptor (GHS-R1a) — this structural class is important because it means MK-677, despite being grouped with peptide secretagogues functionally, is not itself a peptide. It is a small-molecule drug. Merck progressed MK-677 through a substantial clinical development program in the late 1990s and 2000s across multiple indications: frail elderly adults, hip-fracture recovery, growth hormone-deficient adults, pediatric GH deficiency, Alzheimer's disease, and obesity. The 2008 Nass et al. trial (a 2-year RCT in healthy older adults, n=65) remains the most-cited long-duration human dataset for the compound. Despite replicable increases in GH and IGF-1 across trials, Merck ultimately did not secure approval for any indication — the Alzheimer's trial failed, and the modest functional-performance outcomes in the elderly trials did not meet the bar for regulatory approval despite measurable body-composition effects. Merck discontinued development in 1999. The asset was subsequently acquired by Lumos Pharma, which renamed it LUM-201 and has pursued pediatric growth hormone deficiency — a programme that is very much alive as of late 2026 and is the main reason MK-677 may yet become an approved drug. Lumos completed the Phase 2 OraGrowtH210 trial (104 children) and began a 150-child Phase 3 in May 2026 (NCT06948214), with primary completion targeted for December 2027 and a long-term safety extension registered behind it. A second, strikingly contemporary programme is also registered but not yet recruiting: a 202-patient Phase 2 of LUM-201 combined with oral semaglutide versus semaglutide alone, testing whether a GH secretagogue can preserve physical function in adults aged 60 to 85 losing weight on a GLP-1. No approval has resulted yet. MK-677 entered the 'research chemical' and performance-enhancement markets in the 2010s and is now one of the most widely sold non-approved GH-axis compounds online. It is frequently discussed alongside peptide secretagogues (ipamorelin, CJC-1295) because of its shared mechanism and overlapping use cases — though its oral bioavailability, long half-life (~24 hours), and non-peptide structure make it pharmacologically distinct.

How It Works

MK-677 mimics ghrelin, the hunger hormone, by activating the same receptor. This triggers the pituitary gland to release growth hormone. Unlike injectable peptides, it can be taken orally, which is its main practical advantage.

MK-677 is a non-peptide spiropiperidine that acts as a potent, long-acting, orally active agonist of the GHS-R1a receptor. It increases GH secretion by mimicking the GH-stimulating action of endogenous ghrelin. It produces sustained increases in IGF-1 levels. Its effect on cortisol depends on timeframe, and the page-level shorthand that it does not touch cortisol is only half right: the short-term studies found no change at all in 24-hour mean total or free plasma cortisol or urinary free cortisol, but the 2-year trial in older adults recorded a small, statistically significant rise of 47 nmol/L (about 1.7 microg/dL, P=0.020). The honest statement is no meaningful short-term cortisol effect, with a modest elevation emerging over years of continuous use. However, it also activates ghrelin's orexigenic (appetite-stimulating) pathways and can affect glucose homeostasis through GH-mediated insulin resistance.

Evidence Snapshot

Overall Confidence65%

Human Clinical Evidence

Moderate to strong. Multiple human studies demonstrating GH and IGF-1 elevation, body composition effects, and sleep improvement.

Animal / Preclinical

Strong. Well-characterized pharmacology.

Mechanistic Rationale

Strong. GHS-R1a receptor pharmacology is well understood.

Research Gaps & Open Questions

What the current literature has not yet settled about MK-677:

  • 01Long-term (>2 year) human safety beyond the 2008 Nass trial is not characterized; use extending for years — which is common in wellness and performance settings — has no published long-term pharmacovigilance data.
  • 02Carcinogenicity — the sustained IGF-1 elevation over years raises a theoretical tumor-promotion concern that has not been resolved by dedicated long-duration human studies.
  • 03Glucose-tolerance trajectory beyond 2 years is unknown; whether the insulin-resistance effect plateaus, progresses to overt diabetes, or reverses with continued exposure has not been studied.
  • 04Whether cycled dosing (e.g., 12 weeks on, 4 off) actually reduces cumulative metabolic harm vs. continuous dosing has not been tested head-to-head.
  • 05The 2008 trial's lack of functional-performance benefit despite lean-mass gain raises an unresolved question: does the body-composition effect translate to meaningful real-world outcomes in healthy aging, or is it a cosmetic endpoint?
  • 06The congestive heart failure signal that ended the hip-fracture trial early has not been fully mechanistically explained — whether this represents a risk in broader populations is unclear.
  • 07Pediatric long-term safety in GH-deficient children has limited data. The Lumos Pharma programme — MK-677 under the name LUM-201 — entered a 150-child Phase 3 in May 2026 with primary completion due December 2027, so the first adequately powered pediatric efficacy and safety answer is still more than a year away.
  • 08Whether MK-677 can offset the lean-mass loss that accompanies GLP-1 weight loss is now an actual registered question rather than a forum theory: a 202-patient Phase 2 of LUM-201 plus oral semaglutide versus semaglutide alone in adults aged 60 to 85 is registered but not yet recruiting. Given how widely the two are already combined informally, this is the trial most likely to change how MK-677 is used.

Forms & Administration

MK-677 is taken orally, typically once daily. This is its primary advantage over injectable GH secretagogues. Protocols should be determined by a qualified clinician with metabolic monitoring.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

Typical Range

Published human trials have used MK-677 in the 10–25 mg oral daily range, with 25 mg once daily being the dose used in the 2008 Nass 2-year RCT and most long-duration body-composition work. Commonly referenced wellness and performance protocols use 10–25 mg once daily, with 12.5 mg frequently cited as a compromise between efficacy and side-effect tolerability (appetite increase, water retention, glycemic effects scale with dose).

Frequency

Once-daily dosing is sufficient because the half-life is approximately 24 hours — steady-state plasma levels are achieved within about a week of daily dosing. Evening or bedtime administration is most commonly discussed, for two reasons: it aligns with the natural nocturnal GH pulse and can enhance slow-wave sleep; and it pushes peak appetite stimulation into overnight hours rather than during the day. Some users split the dose (morning + evening) to smooth plasma levels and reduce peak-trough appetite swings, but this offers no clear pharmacokinetic advantage. Unlike the peptide GHRPs, MK-677 does not stack synergistically with GHRH analogs the way ipamorelin does — the dual-pathway rationale still applies pharmacologically, but the oral/injectable mismatch and long half-life mean MK-677 is typically used as a standalone rather than in a CJC-1295 stack.

Timing Considerations

Time of day

Bedtime is the most common window to align with the nocturnal GH pulse, but MK-677's ~24-hour half-life means clock time matters less than with injectable GHRPs — consistency day-to-day matters more than the specific hour.

Relative to meals

With or without food. Some users report less next-morning grogginess or appetite-driven sleep disruption when dosed with a small protein-containing snack; others prefer a fully fasted dose.

Relative to exercise

Not tied to training. MK-677 is a daily chronic dosing drug, so workout timing doesn't meaningfully shape the pharmacokinetics.

Cycle Length

Cycling is more commonly discussed for MK-677 than for the injectable secretagogues, precisely because its sustained (non-pulsatile) receptor occupancy raises more concern about pituitary desensitization and chronic metabolic adaptation. Typical protocols run 8–16 weeks on, followed by 4+ weeks off. Continuous multi-year use has been studied in the 2008 Nass trial without evidence of tachyphylaxis, but glucose tolerance and insulin sensitivity do show progressive deterioration over time — meaning 'the GH/IGF-1 effect is sustained' does not mean 'the metabolic cost stays flat.' For users with any baseline insulin resistance, shorter cycles are a prudent precaution.

Protocol Notes

MK-677 is an oral compound, supplied as capsules, tablets, or oral solution. Because it is not a peptide, it does not require reconstitution with bacteriostatic water and does not need to be injected. Oral bioavailability in humans has never been formally characterized — the published record offers only a description of MK-677 as having high oral bioavailability and a long duration of action, with the one concrete figure (above 60%) coming from dogs. Treat the specific percentages that circulate online as unsourced. Most protocols call for taking it on an empty stomach or at bedtime to maximize the GH pulse (elevated insulin and circulating amino acids from a recent meal blunt GH response), though food does not meaningfully block the downstream IGF-1 elevation over days of steady-state dosing. Purity and dosing accuracy of research-chemical MK-677 vary substantially — third-party assay data has repeatedly shown underdosing and occasional cross-contamination in online-sourced product. This quality variance is a material safety concern independent of the pharmacology.

MK-677 is not FDA-approved for any indication. It is sold in the US exclusively as a research chemical labeled 'not for human consumption,' which is not an authorized channel for human use. The numbers above describe commonly-referenced protocols, not a prescription.

Timeline of Effects

Onset

Appetite increase is typically the first noticeable effect, often within 1–3 days of starting dosing — a direct consequence of ghrelin-receptor agonism and independent of the downstream GH/IGF-1 axis. Sleep changes (deeper slow-wave sleep, more REM) follow in the first 1–2 weeks. Body-composition changes (lean mass gain, modest fat-mass reduction) require 4–8+ weeks of consistent use before becoming visible. Water retention and mild extremity puffiness can appear within the first 2 weeks.

Peak Effect

Serum IGF-1 rises progressively over the first 4–8 weeks and plateaus at levels typically 40–90% above baseline (depending on dose and baseline). Body-composition benefits plateau around 3 months in the published literature. Continuous use beyond 6 months shows stable or slowly declining efficacy on subjective markers even as IGF-1 levels remain elevated — a pattern that some users describe as 'blunting' or tachyphylaxis, though whether this is true receptor desensitization or a ceiling effect on the downstream remodeling is unclear. Glucose tolerance tends to worsen progressively with continuous use — this is the clearest dose-duration-related side effect.

After Discontinuation

Endogenous GH pulsatility and ghrelin tone return to baseline within days. IGF-1 returns to pre-treatment levels over 2–4 weeks. Appetite normalizes quickly — often within 3–7 days. Any accumulated lean mass or fat-loss benefits wane over weeks to months depending on training, nutrition, and age. No HPG-axis suppression and no post-cycle therapy requirement. Insulin sensitivity generally recovers over 4–12 weeks off; users with baseline metabolic dysfunction may take longer to renormalize.

Monitoring & Measurement

Bloodwork & Labs

  • •IGF-1 (serum) — reliably rises 40–80% within 4–8 weeks
  • •Fasting glucose and HbA1c — this is the dose-limiting side effect for most users
  • •Fasting insulin (HOMA-IR) — MK-677 produces insulin resistance before fasting glucose climbs, so insulin rises first
  • •Lipid panel
  • •Cortisol and prolactin — expected to remain within reference range at typical doses; a meaningful rise warrants attention

Functional & Performance Tests

  • •DEXA scan — lean mass is the headline endpoint, and MK-677 drives the largest lean-mass gain of any oral secretagogue
  • •Waist circumference
  • •Grip strength
  • •Ankle or pretibial edema check (pinch the skin at the tibia and look for indentation) — water retention is common in the first 2 weeks
  • •Overnight sleep quality via wearable

When to Test

Baseline, 6 weeks, and 12 weeks. If you're insulin-resistant at baseline, add a glucose and insulin check at 2–4 weeks.

Interpretation & Notes

MK-677 reliably lifts IGF-1 by 40–80% within 4–8 weeks and produces the largest lean-mass response of any oral secretagogue. The dose-limiting issue in most users isn't lack of effect — it's glycemic drift. Fasting glucose and HbA1c both tend to rise; if fasting glucose exceeds 110 mg/dL or HbA1c crosses 5.7, pull the dose back or discontinue. Water retention typically settles within 2 weeks; if ankle edema persists, the dose is likely too high. Unlike injectable peptides, MK-677 has drug-like small-molecule pharmacokinetics — hepatic CYP450-mediated metabolism and first-pass clearance make it behave more like a pharmaceutical than a peptide, though the specific isoform involved has never been pinned down in humans. Labs available direct-to-consumer via LabCorp, Quest, Marek Health, and Ulta Lab Tests; interpret with a clinician, especially the insulin-resistance workup.

Common Questions

Is MK-677 actually a peptide?

No. MK-677 is a non-peptide compound (small molecule) that mimics the action of ghrelin at the GHS-R1a receptor. It is discussed alongside peptides because of its mechanism of action.

Why does MK-677 increase appetite?

Because it activates the ghrelin receptor, which is the same receptor that the hunger hormone ghrelin acts on. Increased appetite is one of the most common side effects.

Does MK-677 ruin your insulin sensitivity permanently?

Not permanently, on the available evidence, but the effect is real and it is the single most reliable downside of the compound. It shows up early and it scales with duration: Chapman's 4-week study saw fasting glucose climb from 5.4 to 6.8 mmol/L, and the 2-year Nass trial recorded a 0.3 mmol/L rise with measurably reduced insulin sensitivity. The mechanism is GH-mediated insulin resistance, not damage to the pancreas, and insulin sensitivity generally recovers over roughly 4 to 12 weeks after stopping. Where it becomes genuinely risky is in people who start with prediabetes, metabolic syndrome or type 2 diabetes, because MK-677 pushes an already-impaired system further in the wrong direction. Anyone using it should be tracking fasting insulin as well as glucose — insulin rises before glucose does.

Can you take MK-677 alongside a GLP-1 like semaglutide or tirzepatide?

People do it, on the theory that MK-677's lean-mass effect offsets the muscle loss that accompanies rapid GLP-1 weight loss, and the two drugs pull appetite in opposite directions, which some find helpful and others find simply cancels out. The honest status is that this is now a registered research question rather than a settled practice: Lumos Pharma has registered a 202-patient Phase 2 of LUM-201 (MK-677) plus oral semaglutide versus semaglutide alone in adults aged 60 to 85, aimed at physical function. It has not started. There is a real pharmacological tension to be aware of — GLP-1 drugs improve glycemic control while MK-677 reliably worsens it, so combining them without monitoring glucose and insulin is unwise regardless of the lean-mass rationale.

Is MK-677 legal to buy?

Selling it for human consumption is not legal in the US, though buying it is not what gets prosecuted. It is not FDA-approved for any indication and not a federally controlled substance, so it occupies a gray zone: it is sold as a research chemical labeled not for human consumption, which is not an authorized channel for human use, and FDA has issued warning letters to companies marketing it as a dietary supplement. Ibutamoren mesylate also sits in FDA's Category 2 for both 503A and 503B compounding — substances that may present significant safety risks — so a compounding pharmacy cannot legitimately make it either, and FDA's advisory committee voted 1 to 13 against adding it to the 503A bulks list in October 2024. Australia treats it as Schedule 10, the strictest category. It is banned in sport at all times.

How long does MK-677 take to work?

The effects arrive in a predictable order over different timescales. Appetite is first, often within 1 to 3 days, because that is direct ghrelin-receptor agonism and has nothing to do with growth hormone. Sleep changes follow in the first week or two. Water retention and mild puffiness in the hands and ankles typically show up within the first fortnight and usually settle. IGF-1 climbs over 4 to 8 weeks before plateauing. Visible body-composition change is the slowest piece and needs 8 weeks or more of consistent dosing, and in the one 2-year trial that measured it properly, the lean mass gained did not translate into measurable strength or functional improvement.

Who MK-677 Is NOT For

Contraindications
  • •Active or recent-history cancer — GH and IGF-1 elevation may accelerate proliferation of existing malignancies; chronic IGF-1 elevation is a particular concern given MK-677's sustained dosing profile.
  • •Pregnancy — no human pregnancy safety data; reproductive-toxicology characterization is absent.
  • •Breastfeeding — no data on transfer into breast milk or effects on nursing infants.
  • •Type 2 diabetes or significant insulin resistance — MK-677 reliably worsens glucose tolerance and insulin sensitivity; this is its most clinically relevant metabolic effect and is more pronounced than with injectable secretagogues.
  • •Prediabetes or metabolic syndrome — same rationale; at minimum, use requires monitoring of HbA1c, fasting glucose, and insulin.
  • •Pediatric use outside a diagnosed GH deficiency managed by a pediatric endocrinologist.
  • •Active acromegaly or pituitary adenoma — further stimulation of GH-producing cells is contraindicated.
  • •Congestive heart failure — a Merck Phase IIb trial in elderly hip-fracture patients was terminated early because of a congestive heart failure safety signal, and FDA cites that signal in keeping ibutamoren on its compounding Category 2 list.
  • •Uncontrolled hypertension or moderate-to-severe sleep apnea — GH-mediated fluid retention and upper-airway effects can worsen both.
  • •Known hypersensitivity to spiropiperidine compounds or excipients.

Drug & Supplement Interactions

MK-677 has more documented interaction data than the peptide secretagogues because it went through a substantial Merck clinical program. Because it is a small-molecule compound metabolized hepatically, CYP450-mediated interactions apply that do not apply to peptide secretagogues. Metabolism is CYP450-mediated, but the specific isoform has not been established in humans and the commonly repeated claim that CYP3A4 is the primary pathway is not supported by the regulatory record. The only metabolism data FDA cites comes from equine liver microsomes and thoroughbred horses, which showed phase I metabolism primarily by oxidation and phase II primarily by glucuronidation, without identifying a human isoform. On that basis, caution with strong CYP450 inhibitors (ketoconazole, clarithromycin, ritonavir, large quantities of grapefruit juice) and inducers (rifampin, phenytoin, carbamazepine, St. John's Wort) is a reasonable precaution rather than a characterized interaction, and no formal dose-adjustment guidance exists. Glucose-regulating medications are the most clinically relevant interaction. Insulin, sulfonylureas, GLP-1 agonists, and SGLT2 inhibitors interact with MK-677's GH-mediated worsening of insulin sensitivity — patients on these agents may see elevated HbA1c and fasting glucose that require dose adjustment over weeks. Corticosteroids blunt somatotroph response and attenuate MK-677's GH effect. Somatostatin analogs (octreotide, lanreotide) pharmacologically antagonize it. Opioids and SSRIs have more documented ghrelin-pathway interactions with MK-677 than with injectable GHRPs — chronic opioid exposure can alter ghrelin tone, and serotonergic agents have been shown in preclinical work to modulate GHS-R signaling. Clinical significance is not precisely quantified. Oral estrogens reduce hepatic IGF-1 generation and can blunt the apparent IGF-1 response to MK-677 in labs. Any concurrent medications should be disclosed to the prescribing clinician.

Safety Profile

Safety Information

Common Side Effects

Increased appetiteWater retentionElevated blood sugarLethargyJoint pain

Cautions

  • • May worsen insulin resistance
  • • Not appropriate for diabetics without careful monitoring
  • • Can significantly increase appetite
  • • May elevate prolactin in some individuals

What We Don't Know

Long-term metabolic effects, particularly on insulin sensitivity, require further study. It has not received FDA approval.

Myths & Misconceptions

Myth

MK-677 is a peptide.

Reality

It is not. MK-677 is a non-peptide small-molecule spiropiperidine. It is grouped with peptide secretagogues because it acts at the same ghrelin receptor (GHS-R1a), but structurally and pharmacokinetically it is a conventional small-molecule drug — orally bioavailable, hepatically metabolized through CYP450 oxidation and glucuronidation, and long-acting enough to support once-daily dosing rather than the minutes-to-hours half-life of peptide GHRPs. (The frequently quoted ~24-hour half-life is consistent with once-daily dosing but is not a figure the published record actually reports, and the specific CYP isoform has not been established in humans.) This distinction matters for drug interactions and for regulatory categorization.

Myth

MK-677 is a SARM.

Reality

It is not a selective androgen receptor modulator. MK-677 has no direct action at the androgen receptor and does not affect testosterone production. It is often bundled with SARMs in research-chemical retail catalogs, but the pharmacology is entirely different — MK-677 works through GH/IGF-1, not androgen signaling.

Myth

MK-677 is FDA-approved for adult GH deficiency.

Reality

It is not approved for any indication. Merck developed it through Phase II/III for multiple indications including GH deficiency, frail elderly, and Alzheimer's, but none resulted in approval. It is not a licensed drug in any major jurisdiction.

Myth

MK-677's appetite increase only affects users psychologically — it's just 'thinking about food more.'

Reality

The appetite increase is a direct pharmacological effect of ghrelin-receptor agonism — the same receptor that drives endogenous hunger signaling. Users routinely report a meaningful and sometimes difficult-to-manage increase in food-seeking behavior, not a cognitive reframing. This is why MK-677 is particularly poorly suited for cutting-phase body-composition goals despite its lean-mass preservation effects.

Myth

MK-677 is 'like oral HGH.'

Reality

It produces elevated GH and IGF-1 levels via endogenous pathways and preserves feedback regulation, which is mechanistically different from flat exogenous rhGH dosing. But the comparison oversimplifies: MK-677's sustained receptor occupancy produces a flatter GH profile than injectable GHRPs, its glycemic cost is higher than rhGH at comparable IGF-1 elevation, and the small-molecule pharmacokinetics and drug-interaction profile make it behave like a drug, not a peptide. 'Oral GH secretagogue' is accurate; 'oral HGH' is misleading.

Myth

MK-677 is undetectable in drug testing.

Reality

LC-MS/MS methods for detecting MK-677 and its metabolites in urine are well-established in anti-doping labs, including equine-sports testing, and it is named by name in WADA S2.2.4 on both the 2026 and 2027 lists. The urine window of several days is the floor, not the ceiling: 2026 work extended detection into hair, where a single 10 mg dose left 1.3 pg/mg and a 90-day regimen left 224 pg/mg, and into dried blood spots at sub-nanogram levels. A clean urine test says nothing about whether someone used MK-677 across a training block.

Published Research

27 studies

Peptide Supplements and Their Therapeutic Applications in Sports Medicine.

ReviewPMID: 42578445

Rapid and harmonized analytical workflow for the determination of peptidic and non-peptidic doping agents in dried and liquid blood matrices

Analytical MethodPMID: 42328738

Spontaneous Splenic Rupture in a Patient With Recent Use of Performance-Enhancing Compounds: A Case Report

Case ReportPMID: 42064485

Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677)

Kintz and Gheddar, Clin Chim Acta 2026. Moves MK-677 detection from urine into hair, which changes the retrospective window from days to months: a single 10 mg dose left 1.3 pg/mg in hair, while a 90-day regimen left 224 pg/mg. The practical implication is that a negative urine test no longer says much about whether someone has used MK-677 over a training block.

Analytical MethodPMID: 40882886

LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report

Case ReportPMID: 36303408

Characterization of growth hormone secretagogue small molecule ibutamoren (MK-0677) and its possible metabolites in thoroughbred horses for doping control

PreclinicalPMID: 35716382

Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren

PreclinicalPMID: 34737341

Characterization of equine liver microsome-generated metabolites of growth hormone secretagogue small molecule ibutamoren

PreclinicalPMID: 34542924

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats

PreclinicalPMID: 30450851

The Safety and Efficacy of Growth Hormone Secretagogues.

ReviewPMID: 28400207

MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.

The trial that effectively ended MK-677's development and the reason FDA still lists ibutamoren as a compounding safety risk. The study was terminated early due to a safety signal of congestive heart failure in a limited number of patients, and the authors concluded that MK-0677 has an unfavorable safety profile in this population. Anyone weighing the compound should read this before the body-composition trials.

Clinical TrialPMID: 21067829

Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.

Clinical TrialPMID: 19015485

Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial

Nass et al., 2008 — the definitive long-duration dataset (n=65, ages 60-81). Fat-free mass fell 0.5 kg on placebo and rose 1.1 kg on MK-677, a 1.6 kg between-group difference; the figure quoted elsewhere as a gain is that difference, not a within-group result. GH and IGF-1 reached young-adult levels and stayed there. The trial is equally important for what it did not show and what it did: increased fat-free mass produced no change in strength or function, no difference emerged in visceral or total fat, body weight rose 2.7 kg, fasting glucose rose 0.3 mmol/L (P=0.015) with reduced insulin sensitivity, and cortisol rose 47 nmol/L (P=0.020).

Randomized Controlled TrialPMID: 18981485

The effect of treatment with the oral growth hormone (GH) secretagogue MK-677 on GH isoforms

Randomized Controlled TrialPMID: 12550076

Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children

Randomized Controlled TrialPMID: 11452249

Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women

Randomized Controlled TrialPMID: 11238495

Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677

Randomized Controlled TrialPMID: 10468903

Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group.

Clinical TrialPMID: 10404019

Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a)

Randomized Controlled TrialPMID: 10372705

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males

Randomized Controlled TrialPMID: 9661080

Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure

The pivotal short-term body-composition trial: 8 weeks of MK-677 in obese subjects significantly increased fat-free mass and 24-hour GH secretion, with IGF-1 rising approximately 40%. One nuance usually dropped when this study is cited — the rise in basal metabolic rate was transient, significant at 2 weeks but no longer so at 8 (P=0.1), so this is not evidence of a durable metabolic-rate increase.

Randomized Controlled TrialPMID: 9467542

MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.

Clinical TrialPMID: 9467534

Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man

Copinschi et al., 1997 — the direct evidence behind the sleep effects users report, and the two age groups responded differently. In eight young subjects, high-dose MK-677 raised stage IV sleep duration by about 50% and REM by more than 20%. In six older subjects aged 65 to 71, it raised REM by nearly 50% and shortened REM latency. Deviations from normal sleep fell from 42% to 8% in the young cohort.

Clinical TrialPMID: 9349662

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

Randomized Controlled TrialPMID: 9329386

Determination of a novel growth hormone secretagogue (MK-677) in human plasma at picogram levels by liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry

PreclinicalPMID: 9200526

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 et al., 1996 — the source of the two figures most often quoted about MK-677. In 32 healthy adults aged 64 to 81, 25 mg daily raised mean 24-hour GH concentration by 97 plus or minus 23% and lifted IGF-1 from 141 to 219 micrograms/L at two weeks and 265 at four, restoring it to young-adult range. The same trial recorded the cost: fasting glucose rose from 5.4 to 6.8 mmol/L by week four (P<0.01). Cortisol did not change; prolactin rose 23% but stayed in range.

Randomized Controlled TrialPMID: 8954023

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 et al., 1996. Nine healthy young men, 7 days at 5 and 25 mg. The result is more interesting than it is usually reported: total GH secreted was similar across placebo and both doses, and what changed was GH pulse frequency, driven mainly by extra low-amplitude pulses. IGF-1 rose dose-dependently. Cortisol was explicitly unaffected — 24-hour mean total and free plasma cortisol and urinary free cortisol were all similar under every condition.

Randomized Controlled TrialPMID: 8768828

Quick Facts

Class
Growth Hormone Secretagogue
Tier
B
Evidence
Moderate
Safety
Moderate Data
Updated
Nov 2026
Citations
27PubMed

Also known as

IbutamorenNutrobalMK-0677Ibutamoren mesylateLUM-201

Tags

Growth HormoneBody CompositionSleepAppetiteOral

Peptide Families

Growth Hormone Secretagogues

Related Goals

Body CompositionSleep & Mood

Conditions Discussed

Sarcopenia

Evidence Score

Overall Confidence65%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.