MK-677 (Ibutamoren): Growth Hormone Secretagogue

MK-677, also known as ibutamoren mesylate, occupies a unique position in the peptide research space. Despite being regularly discussed alongside peptides, it's not technically a peptide at all — it's a non-peptide, orally active growth hormone secretagogue that mimics the action of ghrelin. This distinction matters because it gives MK-677 a significant advantage over traditional growth hormone-releasing peptides: you can swallow it rather than inject it.

Developed by Merck in the 1990s, MK-677 was designed to address growth hormone deficiency without the inconvenience of daily injections. The compound successfully raises both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels to those seen in younger adults, and it maintains this effect for years. Clinical trials have followed subjects for up to two years, tracking changes in body composition, sleep architecture, bone metabolism, and metabolic health.

The research tells a complex story. On one hand, MK-677 reliably improves fat-free mass, boosts REM and deep sleep by up to 50%, and reverses diet-induced muscle wasting. On the other, it increases insulin resistance, raises fasting glucose, and contributed to early termination of a hip fracture trial due to congestive heart failure concerns. Despite extensive clinical development, Merck discontinued the project in 1999, and the compound never received FDA approval for any indication.

This guide examines what more than 20 years of research has revealed about MK-677 — how it works, what the clinical trials actually show, and what the safety data means for anyone considering its use.

Table of Contents

• Quick Facts
• What Is MK-677?
• How MK-677 Works
• Clinical Research Overview
  • Growth Hormone and IGF-1 Stimulation
  • Body Composition Changes
  • Sleep Quality Improvements
  • Bone Metabolism Effects
  • Metabolic and Glucose Effects
  • Appetite and Weight Changes
  • Hip Fracture Recovery Trial
  • Alzheimer's Disease Studies
• Safety Profile and Side Effects
• Legal Status and Regulatory Context
• Frequently Asked Questions
• Bottom Line
• References

Quick Facts

Property	Details
Full Name	Ibutamoren mesylate
Other Names	MK-0677, L-163,191, LUM-201
Classification	Non-peptide growth hormone secretagogue
Molecular Formula	C₂₇H₃₆N₄O₅S (free base)
Molecular Weight	528.67 g/mol (free base); 624.77 g/mol (mesylate salt)
Route of Administration	Oral
Bioavailability	>60%
Half-Life	~4.7 hours (terminal elimination); ~24 hours (biological activity)
Developer	Merck & Co.
Current Development	Discontinued by Merck (1999); under investigation as LUM-201 by Lumos Pharma
FDA Status	Not approved; Investigational New Drug (IND)
WADA Status	Prohibited at all times (S2.2.4)

What Is MK-677?

MK-677 is a spiropiperidine compound that functions as a selective agonist of the growth hormone secretagogue receptor (GHS-R1a), also known as the ghrelin receptor. The compound was synthesized in the 1990s by Merck & Co. as part of a research program aimed at developing orally bioavailable alternatives to injectable growth hormone and growth hormone-releasing peptides.

The key innovation was oral activity. Prior growth hormone secretagogues like GHRP-2 and GHRP-6 required injection due to poor oral bioavailability. MK-677's non-peptide structure resists digestive breakdown, allowing it to be absorbed intact from the gastrointestinal tract.

While commonly grouped with peptides due to its similar mechanism of action, MK-677 is chemically distinct. It's a small molecule drug, not a chain of amino acids. This structural difference gives it stability in the digestive system that true peptides lack.

The compound underwent extensive clinical testing from the mid-1990s through the late 2000s. Merck conducted Phase II trials in elderly adults, growth hormone-deficient children, and patients recovering from hip fracture. Despite promising effects on body composition and growth hormone secretion, the company discontinued development in 1999. The reasons for discontinuation were not publicly disclosed, but subsequent safety concerns in the hip fracture trial suggest metabolic and cardiovascular risks may have played a role.

Today, Lumos Pharma is developing the compound as LUM-201 for pediatric growth hormone deficiency. The FDA granted it Orphan Drug Designation, a status reserved for drugs treating rare diseases affecting fewer than 200,000 people in the United States.

How MK-677 Works

MK-677 works by mimicking ghrelin, the "hunger hormone" that your stomach releases when you need food. Ghrelin does more than trigger appetite — it's also one of the most potent natural stimulators of growth hormone release. MK-677 binds to the same receptor (GHS-R1a) located in two key areas of the brain: the hypothalamus and the pituitary gland.

When MK-677 activates these receptors, it triggers the pituitary to release growth hormone in a pulsatile pattern that resembles the body's natural rhythm. Unlike exogenous growth hormone injections that provide a steady flood of hormone, MK-677 stimulates your own pituitary to produce and release GH in bursts, similar to what happens naturally during deep sleep.

This stimulation of endogenous GH production has an important downstream effect: the liver responds to increased growth hormone by producing more insulin-like growth factor 1 (IGF-1). IGF-1 is where many of growth hormone's effects actually occur. It mediates muscle protein synthesis, bone formation, fat metabolism, and numerous other anabolic processes throughout the body.

One notable feature of MK-677 is that it doesn't suppress your body's own growth hormone production. Many compounds that increase hormone levels trigger negative feedback loops that shut down natural production. MK-677 appears to work alongside, rather than against, the body's regulatory systems. The likely mechanism is that IGF-1 provides some negative feedback that prevents excessive GH production, creating a self-limiting system.

The pharmacokinetics also contribute to MK-677's unique profile. After oral administration, the compound is rapidly absorbed and reaches peak plasma levels in 1-2 hours. The terminal elimination half-life is about 4.7 hours, but growth hormone levels remain elevated for approximately 24 hours after a single dose. This extended duration of action means once-daily dosing is sufficient to maintain elevated GH and IGF-1 throughout the day.

MK-677's activation of ghrelin receptors explains both its benefits and its side effects. The same receptor activation that drives GH release also stimulates appetite and influences glucose metabolism, which is why increased hunger and insulin resistance are among the most common adverse effects.

Unlike CJC-1295 and Ipamorelin, which work through different pathways to stimulate GH release, MK-677 specifically targets the ghrelin receptor. This gives it a distinct side effect profile and therapeutic potential compared to other growth hormone secretagogues.

Clinical Research Overview

MK-677 has been studied in more than 600 adult patients across multiple clinical trials spanning up to two years. The research covers a diverse range of populations including healthy elderly adults, growth hormone-deficient children, patients recovering from hip fracture, and individuals with Alzheimer's disease. This section reviews the major findings from published clinical studies.

Growth Hormone and IGF-1 Stimulation

The most consistent finding across all MK-677 studies is robust stimulation of both growth hormone and IGF-1 levels. A study in growth hormone-deficient adults found that 50 mg of MK-677 increased 24-hour mean GH concentrations by 82 ± 29% and IGF-I concentrations by 79 ± 9% compared to baseline. These increases brought hormone levels into the range typically seen in healthy young adults.

In elderly subjects (ages 64-76), daily administration of 25 mg MK-677 increased mean serum IGF-1 concentration from 188 ± 19 ng/mL at baseline to 264 ± 31 ng/mL during treatment — a 40% increase. Growth hormone levels showed even more dramatic responses, with peak GH after single-dose administration reaching 55.9 ± 31.7 μg/L compared to approximately 9 μg/L with placebo.

A key finding is that MK-677 increased the amplitude of GH pulses rather than simply raising baseline levels. This pulsatile pattern more closely resembles physiological GH secretion than the steady-state levels produced by exogenous GH injections.

The two-year study in healthy older adults demonstrated that these effects persist long-term. GH and IGF-1 remained elevated throughout the entire 24-month treatment period, with no evidence of tolerance or receptor desensitization. When participants stopped taking MK-677, hormone levels returned to baseline within weeks.

In growth hormone-deficient children, MK-677 showed comparable efficacy to injectable human growth hormone. Annualized height velocity was 8.0 cm/year at one year with ibutamoren versus 8.6 cm/year with standard GH injections — a clinically insignificant difference. At two years, height velocity was 7.5 cm/year with ibutamoren compared to 6.9 cm/year with injectable GH.

Body Composition Changes

The most significant body composition change observed with MK-677 is an increase in fat-free mass (FFM). In the two-year study of healthy elderly adults, participants taking 25 mg daily gained an average of 1.1 kg of FFM over 12 months, while the placebo group lost 0.5 kg (p<0.001). When comparing MK-677 to placebo, the net difference in FFM was 1.6 kg.

In younger obese males treated for two months, MK-677 produced even more substantial changes. Fat-free mass increased by 1.8 kg in the MK-677 group, and basal metabolic rate rose by an average of 91 kcal/day, suggesting increased metabolic activity accompanying the gain in lean tissue.

However, these gains in lean mass did not translate to measurable improvements in muscle strength or physical function in elderly populations. The two-year study found no significant changes in grip strength, stair climbing ability, or other functional performance measures. This disconnect between body composition changes and functional outcomes suggests that the increased FFM may include water retention or connective tissue rather than contractile muscle protein.

Fat mass changes were inconsistent across studies. Some trials reported modest decreases in body fat percentage, while others found no significant change. The elderly cohort study showed no significant difference in total fat mass between MK-677 and placebo groups over 12 months.

One study specifically examined the effects of MK-677 on diet-induced catabolism. During a seven-day period of caloric restriction (18 kcal/kg body weight per day, 20% protein), participants receiving 25 mg MK-677 daily maintained nitrogen balance at 0.31 g/day, while the placebo group experienced negative nitrogen balance of -1.48 g/day (p<0.01). This demonstrates that MK-677 can effectively counteract muscle protein breakdown during periods of inadequate calorie or protein intake.

Sleep Quality Improvements

Some of the most robust findings with MK-677 concern sleep architecture. A controlled study published in Neuroendocrinology examined prolonged oral treatment with MK-677 and found substantial improvements in sleep quality across age groups.

In young subjects (ages 18-30), high-dose MK-677 (25 mg) produced approximately a 50% increase in stage IV sleep (deep, slow-wave sleep) and more than a 20% increase in REM sleep compared to placebo. These are clinically significant changes — stage IV sleep is when growth hormone is naturally secreted and when tissue repair and immune function are most active.

In older adults (ages 65-71), the effects on REM sleep were even more pronounced. MK-677 treatment was associated with a nearly 50% increase in REM sleep duration and a significant decrease in REM latency (the time it takes to enter REM sleep after falling asleep). Under placebo conditions, 42% of elderly participants showed deviations from normal sleep patterns; this dropped to just 8% under high-dose MK-677 treatment.

The sleep improvements appear to be a direct result of increased growth hormone secretion. Growth hormone and slow-wave sleep have a bidirectional relationship — GH is released primarily during deep sleep, and GH itself promotes deeper sleep. By amplifying the body's GH pulses, MK-677 appears to strengthen this natural cycle.

Many users report more vivid dreams when taking MK-677, which aligns with the documented increases in REM sleep. REM is the sleep stage most associated with vivid, narrative dreaming.

Unlike sleep medications that often impair sleep architecture while increasing total sleep time, MK-677 appears to improve both sleep quality and quantity without obvious next-day sedation or cognitive impairment.

These sleep benefits may be among MK-677's most practical advantages, particularly for older adults who experience age-related decline in sleep quality and GH secretion.

Bone Metabolism Effects

MK-677's effects on bone health have produced mixed results. The compound consistently increases biochemical markers of bone turnover, but actual improvements in bone mineral density (BMD) have been disappointing in most studies.

In healthy elderly adults, nine weeks of treatment with 25 mg MK-677 increased serum osteocalcin (a marker of bone formation) by 29.4% and bone-specific alkaline phosphatase by 10.4%. At the same time, urinary N-telopeptide (NTX) excretion — a marker of bone resorption — increased by 22.6%. This pattern suggests MK-677 increases bone turnover in both directions rather than selectively favoring bone formation.

In obese young males, short-term treatment (two weeks) with MK-677 increased carboxy-terminal propeptide of type I procollagen (a bone formation marker) by 23%, again demonstrating clear biochemical effects on bone metabolism.

However, these biochemical changes have not consistently translated to improvements in bone mineral density. The two-year study in elderly adults found that femoral neck BMD actually decreased by 0.005 g/cm² in the MK-677 group, while it increased by 0.012 g/cm² in the placebo group — a small but statistically significant difference favoring placebo. There were no significant differences in spine or total hip BMD.

An 18-month study examined MK-677 alone, alendronate alone, and the combination in postmenopausal osteoporotic women. The combination did not enhance BMD at any skeletal site compared to alendronate alone. Interestingly, MK-677 did attenuate alendronate's suppressive effect on bone formation markers, suggesting it maintained some anabolic activity even when paired with an antiresorptive drug.

The disconnect between bone turnover markers and actual BMD changes remains unexplained. One possibility is that the simultaneous increase in both bone formation and bone resorption produces no net gain in bone mass. Another is that longer treatment durations might eventually produce measurable BMD improvements, but existing studies haven't extended beyond two years.

For comparison, Tesamorelin, an FDA-approved GHRH analog, has shown more favorable effects on bone in some populations, though direct head-to-head comparisons don't exist.

Metabolic and Glucose Effects

One of the most concerning findings from MK-677 research is its consistent negative effect on insulin sensitivity and glucose metabolism. This is a predictable consequence of elevated growth hormone, which is known to have diabetogenic effects.

In the two-year study of healthy elderly adults, fasting serum glucose increased by an average of 0.28 mmol/L (approximately 5 mg/dL) in the MK-677 group compared to placebo — a statistically significant but relatively modest increase. More concerning was the decline in insulin sensitivity measured by homeostatic model assessment.

A study examining metabolic effects in elderly subjects found that both growth hormone and MK-677 increased insulin resistance and blood glucose. By 12 months, fasting blood glucose and HbA1c (a marker of average glucose levels over 2-3 months) had increased significantly compared to baseline.

The mechanism is well understood. Growth hormone promotes lipolysis (fat breakdown) and increases free fatty acid availability, which impairs insulin signaling in muscle and liver tissue. This leads to compensatory hyperinsulinemia — the pancreas secretes more insulin to maintain normal blood glucose. Over time, this can progress to insulin resistance and potentially type 2 diabetes, particularly in individuals with existing metabolic dysfunction.

Growth hormone also directly antagonizes insulin action in peripheral tissues, creating an immediate glucose-raising effect even before chronic insulin resistance develops.

For individuals with pre-existing insulin resistance, metabolic syndrome, or type 2 diabetes, MK-677 use could exacerbate these conditions and increase cardiovascular risk. The clinical trials excluded participants with uncontrolled diabetes for this reason.

Despite these metabolic concerns, the magnitude of glucose elevation in most studies was relatively small, and many participants completed two years of treatment without developing overt diabetes. However, the long-term metabolic consequences of sustained growth hormone elevation via MK-677 remain incompletely characterized, particularly in at-risk populations.

This metabolic profile differs somewhat from Sermorelin, which tends to produce more modest GH elevations and may have a less pronounced effect on glucose metabolism.

Appetite and Weight Changes

MK-677's stimulation of ghrelin receptors produces predictable effects on appetite. Across multiple studies, increased appetite was one of the most commonly reported side effects, though the magnitude and duration varied.

In the two-year study of elderly adults, increased appetite was the most frequent adverse event, occurring in 67% of MK-677 participants versus 36% of placebo participants. However, this effect tended to diminish over time. Many participants reported that the appetite stimulation was most pronounced during the first few months of treatment and gradually subsided, even while continuing the medication.

This appetite stimulation can be viewed as either a benefit or a drawback depending on the context. For elderly individuals with physiological anorexia and unintended weight loss, increased appetite could support nutritional intake and preservation of lean body mass. For individuals concerned about body composition or trying to maintain a caloric deficit, constant hunger would be problematic.

Interestingly, despite significant increases in appetite, most studies did not observe proportional increases in body weight. The elderly cohort gained an average of 1.1 kg of fat-free mass but did not show large increases in fat mass over 12-24 months. This suggests that the increased calorie intake may have been offset by increased metabolic rate (likely due to increased lean body mass and elevated GH).

In studies of caloric restriction, MK-677's appetite-stimulating effects were explicitly noted as a potential confound — researchers had to carefully monitor food intake to ensure participants in the MK-677 group didn't simply eat more, which would have invalidated the catabolic condition the study was designed to examine.

The ghrelin-mimetic properties that drive appetite also likely contribute to some of MK-677's beneficial effects on body composition and metabolism. Ghrelin signaling influences not just hunger but also nutrient partitioning, adipose tissue metabolism, and systemic energy balance.

For individuals using MK-677 in performance or body composition contexts, the appetite increase can be managed through strategies like taking the dose before bed (to sleep through the peak hunger window) or using the increased appetite strategically during bulking phases.

Hip Fracture Recovery Trial

One of the most significant MK-677 clinical trials was a Phase IIb multicenter study in patients recovering from hip fracture — a population where improved muscle mass and functional recovery could meaningfully reduce morbidity and mortality. The results were disappointing and raised important safety concerns.

The trial randomized 123 patients aged 60 years or older who had recently undergone hip fracture repair to receive either 25 mg MK-677 daily or placebo for 24 weeks. The primary endpoints were functional recovery measures, including walking speed, stair climbing, and activities of daily living.

Despite successfully increasing serum IGF-1 levels (the biochemical confirmation that MK-677 was pharmacologically active), the treatment did not produce significant improvements in most functional performance measures. The study found no meaningful differences between groups in walking speed, muscle strength, or overall functional recovery.

There was one potentially positive signal: the MK-677 group experienced fewer falls during the study period compared to placebo (p = 0.096), though this did not quite reach statistical significance. Whether this reflected improved balance, increased caution due to appetite side effects, or random variation remains unclear.

More concerning, the trial was terminated early due to a safety signal of congestive heart failure in a limited number of patients. While the absolute number of heart failure cases was small, the imbalance between treatment and placebo groups was sufficient to halt enrollment and prompt a reassessment of MK-677's safety profile in elderly patients with comorbidities.

This finding is particularly relevant because hip fracture patients are often frail elderly individuals with multiple cardiovascular risk factors. The mechanism by which MK-677 might increase heart failure risk is not fully elucidated, but possibilities include fluid retention (a known effect of growth hormone), increased cardiac workload due to increased lean body mass, or exacerbation of underlying cardiac dysfunction.

Following this trial, the FDA and researchers concluded that MK-677 has an unfavorable safety profile in hip fracture patients and likely in other frail elderly populations with cardiovascular comorbidity. This substantially narrowed the potential therapeutic window for the compound and likely contributed to Merck's decision to discontinue development.

Alzheimer's Disease Studies

MK-677 was also evaluated as a potential treatment for Alzheimer's disease, based on the hypothesis that restoring youthful levels of growth hormone and IGF-1 might slow cognitive decline. The rationale was that GH and IGF-1 have neuroprotective effects, support synaptic plasticity, and decline with age in parallel with cognitive function.

A large, double-blind, multicenter trial randomized 563 patients with mild to moderate Alzheimer's disease to receive either ibutamoren or placebo daily for 12 months. The primary endpoints were cognitive function measured by standard neuropsychological testing batteries and overall clinical progression of dementia.

The results were negative. MK-677 had no clinical effect on Alzheimer's disease progression. There were no significant differences between the treatment and placebo groups in cognitive test scores, functional abilities, or behavioral symptoms at the end of the 12-month study period.

This negative result is particularly notable because MK-677 successfully increased growth hormone secretion in these patients, confirming the drug was pharmacologically active. The problem wasn't that the compound failed to hit its biochemical target — it simply didn't translate into clinical benefit for Alzheimer's patients.

Several explanations are possible. First, the hypothesis that GH/IGF-1 restoration would improve cognition may be incorrect — correlation between hormone decline and cognitive decline doesn't prove causation. Second, Alzheimer's pathology (amyloid plaques, tau tangles, neuroinflammation) may be too advanced by the time of clinical diagnosis for metabolic interventions to help. Third, peripheral GH elevation may not adequately increase brain IGF-1 levels due to limited blood-brain barrier penetration.

This negative trial effectively eliminated Alzheimer's disease as a development path for MK-677, adding to the growing list of failed amyloid-independent therapeutic strategies for dementia.

Safety Profile and Side Effects

MK-677 has been administered to more than 600 adult subjects for durations ranging from weeks to two years, providing a reasonable database for characterizing its safety profile. The compound is generally well tolerated at standard doses (25 mg daily), but several consistent adverse effects and some serious safety concerns have emerged.

Common Side Effects

Increased Appetite: The most frequent side effect, reported by approximately 67% of participants in controlled trials compared to 36% on placebo. This is a direct pharmacological consequence of ghrelin receptor activation. The effect tends to be most pronounced during the first few months and often diminishes with continued use, though it rarely disappears entirely.

Peripheral Edema: Mild to moderate lower-extremity edema (fluid retention in the legs and feet) is common. This is a well-known effect of growth hormone and reflects sodium and water retention. In most cases, the edema is transient and resolves even with continued treatment. In elderly populations and those with cardiovascular disease, however, fluid retention can be more problematic.

Muscle Pain: Some participants report mild muscle aches or joint discomfort, particularly in the early phases of treatment. This may relate to increased growth hormone effects on connective tissue or fluid shifts in joint spaces.

Increased Fasting Glucose and Insulin Resistance: As discussed earlier, MK-677 consistently produces modest increases in fasting blood glucose (average 5 mg/dL) and decreases in insulin sensitivity. These changes are generally subclinical in healthy individuals but could accelerate progression to type 2 diabetes in at-risk populations.

Elevated HbA1c: In long-term studies, glycated hemoglobin (HbA1c) increased modestly, reflecting sustained elevation in average blood glucose levels.

Serious Adverse Events

Congestive Heart Failure: The early termination of the hip fracture recovery trial due to an excess of heart failure cases is the most serious safety signal associated with MK-677. While the absolute risk appears to be low in healthy individuals, the data suggest that MK-677 may pose cardiovascular risks in elderly patients with comorbidities or pre-existing heart disease.

Potential for Hyperglycemia: While most study participants did not develop overt diabetes, individuals with pre-existing impaired glucose tolerance or diabetes could experience clinically significant hyperglycemia requiring adjustment of diabetes medications.

Hepatotoxicity: There is at least one published case report of hepatotoxicity (liver injury) induced by MK-677 use. The report describes elevated liver enzymes that resolved after discontinuation. While single case reports don't establish causation, they suggest liver function monitoring may be prudent during extended use.

Cancer Risk

Given that growth hormone and IGF-1 promote cell proliferation, theoretical concerns exist about whether long-term MK-677 use might increase cancer risk. The available data provide some reassurance but are not definitive.

As of a 2007 review, more than 600 adult patients had been exposed to MK-677 for 6-12 months. The combined incidence rate for malignancies in any MK-677 treatment group was similar to the incidence rate in placebo groups. No signal suggesting increased cancer risk emerged during clinical development.

However, these studies were neither long enough nor large enough to detect modest increases in cancer risk, particularly for cancers with long latency periods. Individuals with known or suspected hormone-sensitive cancers should avoid MK-677 due to its effects on the GH/IGF-1 axis.

Comparison with Other GH Secretagogues

Compared to injectable peptides like Hexarelin and GHRP-6, MK-677's side effect profile is broadly similar, with the advantage of avoiding injection-site reactions but the disadvantage of more pronounced appetite stimulation due to its ghrelin-mimetic properties.

Unlike direct GH administration, MK-677 works through the body's own regulatory pathways, which may reduce the risk of supraphysiological hormone spikes and associated side effects. However, the clinical data suggest this theoretical advantage has not translated into a dramatically safer profile in vulnerable populations.

Long-Term Safety Uncertainties

The longest controlled trial of MK-677 lasted two years — a substantial duration for clinical research but still limited compared to the decades of exposure that might occur if the compound were used chronically. Long-term consequences of sustained GH/IGF-1 elevation remain incompletely characterized.

Questions that remain unanswered include:

• Does chronic MK-677 use increase lifetime cancer risk?
• What are the long-term cardiovascular effects in healthy adults?
• Does the insulin resistance produced by MK-677 eventually lead to overt type 2 diabetes?
• Are there effects on other hormonal axes (thyroid, adrenal, gonadal) with extended use?

Until these questions are answered through additional research, the risk-benefit calculation for MK-677 remains uncertain, particularly for use outside supervised clinical contexts.

Legal Status and Regulatory Context

MK-677's legal status varies significantly depending on jurisdiction and intended use, but it is not approved for human use anywhere in the world as a prescription medication.

FDA Status

In the United States, MK-677 remains an Investigational New Drug (IND). It has not been approved by the FDA for any medical indication. Merck discontinued development in 1999 without submitting a New Drug Application.

Lumos Pharma is currently developing the compound under the name LUM-201 for pediatric growth hormone deficiency. The FDA has granted it Orphan Drug Designation, which provides regulatory incentives for development of treatments for rare diseases. However, approval is not guaranteed, and clinical trials are still ongoing.

Because MK-677 is not FDA-approved, it cannot legally be prescribed by physicians or marketed as a therapeutic drug. Its sale as a dietary supplement is also illegal, as it does not meet the regulatory definition of a dietary ingredient. Despite this, MK-677 is widely available from research chemical suppliers and underground markets.

The FDA has explicitly warned about MK-677 in dietary supplements, noting that it poses significant safety risks including the potential for congestive heart failure and has not been proven safe or effective for any use.

WADA Prohibition

The World Anti-Doping Agency (WADA) lists MK-677 on its Prohibited List under Section S2.2.4: Growth Hormone Releasing Factors. It is prohibited at all times — both in-competition and out-of-competition — for all athletes subject to WADA testing.

The addition of ibutamoren as a specific example in the 2024 Prohibited List reflects growing detection capabilities and likely increasing use by athletes seeking performance advantages. Any competitive athlete who tests positive for MK-677 faces a multi-year ban from their sport.

Drug testing laboratories can now detect MK-677 use through advanced mass spectrometry techniques. Detection windows depend on dose and frequency of use but can extend for days to weeks after the last dose.

Department of Defense Prohibition

The U.S. Department of Defense lists MK-677 on its Prohibited Dietary Supplement Ingredients list. Military service members are prohibited from using products containing MK-677, and doing so can result in disciplinary action under the Uniform Code of Military Justice.

International Status

No country has approved MK-677 for therapeutic use. It is not available by prescription in Europe, Canada, Australia, or other major pharmaceutical markets.

Some countries classify it as a prescription-only medicine even though no legal prescription pathway exists. Others treat it as an unapproved drug that can be sold for research purposes only. Importation rules vary, with some countries allowing small quantities for personal research use and others prohibiting importation entirely.

Legal Availability

Despite its unapproved status, MK-677 is readily available from online vendors marketing it as a "research chemical" with disclaimers that it is "not for human consumption." These vendors operate in a legal gray area — they're technically not making therapeutic claims or marketing it for human use, but the intended use is obvious.

Purchasing and possessing MK-677 for personal use is not explicitly illegal in most jurisdictions (it's not a scheduled controlled substance), but using it as a drug without medical supervision carries medical and legal risks. Sellers who market it for human use or make therapeutic claims can face FDA enforcement action.

For individuals considering MK-677 use, the lack of regulatory oversight means product purity and dosing accuracy are uncertain. Contamination, mislabeling, and substitution with other compounds are documented problems in the research chemical market.

Future Regulatory Prospects

If Lumos Pharma's development program succeeds and LUM-201 receives FDA approval for pediatric growth hormone deficiency, MK-677 would gain legitimate prescription status for that narrow indication. This would not make it legal for off-label uses like anti-aging or body composition modification, but it would establish a legal supply chain and confirm the compound's manufacturing specifications.

Given the safety concerns that emerged in clinical trials, particularly in elderly populations, it's unlikely MK-677 will ever be approved for broad use in aging adults or for body composition indications.

Frequently Asked Questions

Is MK-677 a peptide or a SARM?

MK-677 is neither a peptide nor a selective androgen receptor modulator (SARM), despite frequently being grouped with both. It's a non-peptide small molecule that functions as a growth hormone secretagogue. It mimics ghrelin by binding to the GHS-R1a receptor, stimulating growth hormone release from the pituitary gland. The confusion arises because it's often sold by the same vendors that market peptides and SARMs, and it's used for similar body composition goals.

How long does it take for MK-677 to work?

The pharmacological effects begin within hours — a single dose produces measurable increases in growth hormone and IGF-1 within 1-2 hours that persist for approximately 24 hours. However, clinically noticeable effects on body composition typically require several weeks to months. In clinical trials, significant increases in fat-free mass were observed after 8-12 weeks of continuous use. Sleep quality improvements are often reported within days to weeks.

What time of day should MK-677 be taken?

Research studies have used both morning and evening dosing with similar hormonal effects. Some users prefer evening dosing (30-60 minutes before bed) for two reasons: it aligns with the body's natural nighttime growth hormone pulse, and it allows them to sleep through the peak appetite stimulation that occurs 1-2 hours after dosing. The long half-life (~24 hours of biological activity) means timing is less critical than with shorter-acting compounds.

Does MK-677 need to be cycled?

Clinical studies administered MK-677 continuously for up to two years without evidence of receptor desensitization or loss of efficacy. Growth hormone and IGF-1 remained elevated throughout the treatment period. From a purely pharmacological standpoint, cycling does not appear necessary to maintain effectiveness. However, some users cycle it to allow insulin sensitivity to recover (reducing long-term metabolic risk) or to assess whether benefits persist after discontinuation.

Can MK-677 cause diabetes?

MK-677 increases insulin resistance and fasting blood glucose — both risk factors for type 2 diabetes. In clinical trials of healthy elderly adults, the average increase in fasting glucose was modest (about 5 mg/dL), and most participants did not develop overt diabetes during 1-2 years of treatment. However, individuals with pre-existing insulin resistance, metabolic syndrome, or prediabetes are at higher risk. Long-term metabolic consequences beyond two years are unknown. Anyone with glucose metabolism concerns should monitor blood glucose and HbA1c regularly if using MK-677.

Does MK-677 increase appetite?

Yes, significantly. Increased appetite is the most common side effect, reported by about two-thirds of users in clinical trials. This is a direct result of MK-677's ghrelin-mimetic activity — ghrelin is the body's primary hunger hormone. The effect is most pronounced during the first few months and tends to diminish but rarely disappears completely. Some people find the appetite increase useful during muscle-building phases, while others struggle with it when trying to maintain a caloric deficit.

Is MK-677 safe for long-term use?

The longest controlled trial of MK-677 lasted two years, during which it was generally well tolerated in healthy elderly adults. However, an earlier trial in hip fracture patients was terminated due to congestive heart failure concerns. Long-term safety data (beyond two years) don't exist. Known risks include insulin resistance, fluid retention, and potential cardiovascular effects, particularly in elderly individuals or those with pre-existing heart conditions. Cancer risk from chronic GH/IGF-1 elevation remains a theoretical concern without definitive long-term data. Until more evidence exists, "long-term safe" remains an unanswered question.

How does MK-677 compare to actual growth hormone injections?

MK-677 stimulates your body's own growth hormone production through pituitary activation, producing pulsatile GH release that mimics natural physiology. Growth hormone injections deliver exogenous hormone directly, creating steady-state levels. Both increase serum GH and IGF-1, but MK-677 offers the advantages of oral administration and preservation of endogenous pulsatile secretion. However, MK-677 cannot match the GH levels achievable with supraphysiological injection doses. In clinical trials comparing ibutamoren to GH injections in children, growth outcomes were similar, suggesting similar efficacy at therapeutic doses.

What's the difference between MK-677 and CJC-1295?

CJC-1295 is a growth hormone-releasing hormone (GHRH) analog that works by binding to GHRH receptors on pituitary cells. MK-677 is a ghrelin mimetic that binds to ghrelin receptors (GHS-R1a). Both stimulate GH release but through different pathways. CJC-1295 requires injection and is often paired with Ipamorelin for synergistic effects, while MK-677 is orally active and works alone. MK-677 has more pronounced appetite stimulation due to its ghrelin-mimetic properties. Both have been studied in clinical research, but MK-677 has substantially more long-term human data.

Bottom Line

MK-677 represents a pharmacological achievement — a non-peptide, orally bioavailable compound that reliably stimulates growth hormone secretion for up to 24 hours from a single dose. Two decades of research have confirmed it can increase GH and IGF-1 to youthful levels, improve fat-free mass, significantly boost REM and deep sleep, and reverse diet-induced muscle wasting. These effects persist for at least two years without evidence of tolerance.

But clinical success requires more than biochemical activity. Despite its ability to raise hormone levels, MK-677 failed to produce meaningful functional improvements in elderly patients recovering from hip fracture. It didn't slow Alzheimer's disease progression. It didn't improve bone mineral density despite increasing bone turnover markers. And concerning safety signals — particularly the congestive heart failure cases that terminated the hip fracture trial — emerged in vulnerable populations.

The metabolic effects are particularly concerning. Every study that examined glucose metabolism found increased insulin resistance and elevated fasting glucose. While the magnitude was modest in healthy subjects, it raises legitimate questions about long-term metabolic consequences, especially given that no data extend beyond two years.

Merck's decision to discontinue development in 1999 likely reflected a calculated assessment that the therapeutic window was too narrow and the safety profile insufficiently favorable for broad clinical use. The compound works — it just doesn't work well enough, for the right indications, with adequate safety margins, to justify approval.

Lumos Pharma's ongoing development for pediatric growth hormone deficiency represents the narrowest viable indication: a population with pathological GH deficiency, limited treatment alternatives, and presumably lower cardiovascular risk than elderly adults. Whether the FDA will approve it for this use remains to be seen.

For those considering MK-677 outside clinical trials, the calculus is complex. The compound has real effects — improved sleep quality alone might justify use for some individuals. But it also has real risks, particularly for anyone with cardiovascular disease, glucose metabolism issues, or other metabolic comorbidities. The long-term consequences of sustained GH/IGF-1 elevation through MK-677 remain unknown.

Unlike compounds like Semaglutide, which received FDA approval based on clear clinical benefits that outweighed known risks, MK-677 exists in regulatory limbo — pharmacologically active but clinically unproven, available but unapproved, effective at changing biomarkers but uncertain in its ability to improve the outcomes that actually matter.

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Disclaimer: This article is for educational and informational purposes only and is not intended as medical advice. MK-677 (ibutamoren) is not approved by the FDA for human use and is classified as an investigational drug. The information presented here is based on published research studies but should not be interpreted as an endorsement or recommendation for use. Any decision to use MK-677 or similar compounds should be made only after consulting with a qualified healthcare provider who can assess individual health status, risk factors, and potential drug interactions. Self-administration of unapproved compounds carries significant medical and legal risks. PeptideJournal.org does not sell peptides or research compounds and has no financial relationships with vendors or manufacturers.

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