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MK-677 Long-Term Studies: Benefits & Risks

*What the clinical trial data actually shows about ibutamoren after months and years of use — including the study that was stopped early.*

What the clinical trial data actually shows about ibutamoren after months and years of use — including the study that was stopped early.

Table of Contents

What Is MK-677 and Why Do Long-Term Studies Matter? {#what-is-mk-677-and-why-do-long-term-studies-matter}

MK-677 (ibutamoren) is an oral compound that mimics the hunger hormone ghrelin. When it binds to ghrelin receptors in the brain, the pituitary gland releases more growth hormone (GH). This in turn raises insulin-like growth factor 1 (IGF-1). Unlike injectable growth hormone, MK-677 is taken by mouth, and it works through the body's own signaling system rather than providing GH directly.

Long-term study data matters here more than with most compounds. Growth hormone levels drop naturally with age — about 14% per decade after age 30. The appeal of MK-677 is sustained GH elevation without daily injections. But growth hormone affects metabolism, insulin sensitivity, cardiovascular function, bone turnover, and cell growth. Raising it chronically could help, or it could cause problems. The only way to know is to study people who take it for months and years.

This article reviews every significant clinical trial of MK-677 lasting eight weeks or longer — what they measured, what they found, and where the risks showed up.

How MK-677 Works {#how-mk-677-works}

MK-677 is a selective agonist of the growth hormone secretagogue receptor (GHSR), the same receptor that ghrelin activates. When MK-677 binds to GHSR in the hypothalamus and pituitary, it triggers pulsatile GH release — the same on-off pattern the body uses naturally. This is different from injecting GH directly, which creates a flat, non-physiological spike.

The downstream effects follow the normal GH cascade:

StepWhat Happens
MK-677 binds GHSRGhrelin receptor activated in the pituitary
GH release increasesPulsatile secretion pattern maintained
Liver produces IGF-1Primary mediator of GH's anabolic effects
IGF-1 acts on tissuesProtein synthesis, bone formation, cell growth

One important note: MK-677 also increases appetite and cortisol to a mild degree, and it affects insulin signaling. These secondary effects become significant in long-term use.

MK-677 is often grouped with SARMs (selective androgen receptor modulators), but it is not a SARM. It does not interact with androgen receptors at all. It is a growth hormone secretagogue — a separate drug class entirely.

Study 1: The Two-Year Landmark Trial in Healthy Older Adults {#study-1-the-two-year-landmark-trial}

Nass R, Pezzoli SS, Oliveri MC, et al. "Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults." Annals of Internal Medicine. 2008;149(9):601–611.

This is the most rigorous MK-677 study ever conducted and the only one to run for two years. The design was a randomized, double-blind, modified-crossover trial with 65 healthy older adults (ages 60–81). Participants received either 25 mg MK-677 or placebo once daily.

Growth Hormone and IGF-1 Results

MK-677 raised both GH and IGF-1 to levels typical of healthy young adults. The increase in pulsatile GH secretion lasted for the full duration of treatment — up to two years — without the response fading over time. When participants stopped taking MK-677, their GH and IGF-1 levels returned to baseline.

This sustained effect was significant. Many hormonal interventions lose potency as the body adapts (tachyphylaxis). MK-677 did not show this problem.

Body Composition

Fat-free mass (FFM) increased by +1.1 kg in the MK-677 group. The placebo group lost -0.5 kg over the same period. The difference was statistically significant (p < 0.001).

However, there is an important caveat. Some researchers believe that part of the "lean mass" gain was intracellular water retention rather than new muscle protein. Growth hormone is known to cause fluid shifts, and the body composition methods used (DEXA) cannot distinguish between water weight and actual contractile tissue.

Strength and Physical Function

Despite the increase in fat-free mass, MK-677 did not improve muscle strength or physical function in any measured test. This disconnect — more mass but no more strength — supports the water-retention hypothesis and has been a consistent finding across MK-677 studies.

Metabolic Effects

Fasting glucose rose by an average of ~5 mg/dL, and insulin sensitivity declined. These changes were statistically significant but described as modest by the researchers. A 2023 review in The Journals of Gerontology characterized the insulin resistance as "very mild" and "not thought to be clinically significant."

Still, in a population already at risk for type 2 diabetes (older adults), even small metabolic shifts warrant attention during extended use.

Study 2: Reversing Diet-Induced Catabolism {#study-2-reversing-diet-induced-catabolism}

Murphy MG, Plunkett LM, Gertz BJ, et al. "MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism." Journal of Clinical Endocrinology & Metabolism. 1998;83(2):320–325.

This study tested whether MK-677 could counteract muscle loss during calorie restriction — a scenario relevant to hospitalized patients, the elderly, and anyone recovering from surgery or illness.

Eight healthy volunteers (ages 24–39) were put on a calorie-restricted diet (18 kcal/kg/day) for two 14-day periods. During the second week of each period, they received either 25 mg MK-677 or placebo.

Key Results

MeasurePlaceboMK-677Significance
Daily nitrogen balance (week 2)-1.48 g/day+0.31 g/dayp < 0.01
Cumulative nitrogen balance (days 8–14)-8.97 g·day+2.69 g·dayp < 0.001
Peak GH response (day 1)~9 μg/L55.9 μg/L—
Mean IGF-1 (last 5 days)188 ng/mL264 ng/mLp < 0.01

Nitrogen balance is a direct measure of whether the body is building or breaking down protein. Negative values mean muscle loss. MK-677 reversed the negative nitrogen balance completely and pushed it slightly positive — meaning participants were retaining protein even while eating significantly fewer calories than they needed.

Cortisol and prolactin levels did not change, which was reassuring — previous GH secretagogues had sometimes raised these hormones in problematic ways.

This remains one of the strongest functional findings for MK-677, though the study was small and short-term.

Study 3: Bone Mineral Density in Postmenopausal Women {#study-3-bone-mineral-density-in-postmenopausal-women}

Murphy MG, Weiss S, McClung M, et al. "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." Journal of Clinical Endocrinology & Metabolism. 2001;86(3):1116–1125.

This was the largest MK-677 trial by participant count: 292 postmenopausal women (ages 64–85) with low bone mineral density. It ran for 18 months and tested four groups: MK-677 alone, alendronate (a standard osteoporosis drug) alone, the combination, and placebo.

Results

  • IGF-1 increased 39–45% in both MK-677 groups (p < 0.05 vs. placebo)
  • Bone turnover markers (osteocalcin, urinary NTx) increased 22% and 41% respectively with MK-677 (p < 0.05 vs. placebo)
  • Femoral neck BMD increased 4.2% with MK-677 + alendronate vs. 2.5% with alendronate alone (p < 0.05)
  • MK-677 + alendronate mitigated the reduction in bone formation markers that alendronate typically causes (-40% vs. -54% osteocalcin decrease; p < 0.05)
  • No significant BMD improvement at the lumbar spine, total hip, or total body for MK-677 vs. alendronate alone

Interpretation

The femoral neck finding is clinically relevant — hip fractures are among the most dangerous fractures in older women. But the fact that improvements didn't extend to other skeletal sites was disappointing. The researchers concluded that the anabolic GH effect via MK-677 could partially counteract alendronate's suppression of bone formation, but the overall benefit did not justify the added side effects of chronic GH elevation.

Study 4: Sleep Quality in Young and Older Adults {#study-4-sleep-quality-in-young-and-older-adults}

Copinschi G, Leproult R, Van Onderbergen A, et al. "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man." Neuroendocrinology. 1997;66(4):278–286.

Sleep and growth hormone are tightly linked. Most daily GH secretion occurs during deep sleep. As people age, both deep sleep and GH decline together. Copinschi's group tested whether raising GH with MK-677 could improve sleep architecture.

Young Subjects (ages 18–30)

Eight young men participated in a crossover design with 5 mg MK-677, 25 mg MK-677, and placebo, each for 7 days. Sleep was measured with polysomnography — the gold standard for sleep research.

  • High-dose MK-677 increased Stage IV (deep) sleep duration by ~50%
  • REM sleep increased by more than 20% (p < 0.05)
  • Sleep deviations from normal patterns dropped from 42% under placebo to 8% under MK-677 (p < 0.03)

Older Subjects (ages 65–71)

Six older adults received 2 mg and 25 mg MK-677 over two 14-day treatment periods.

  • REM sleep increased by nearly 50% (p < 0.05)
  • REM latency decreased (p < 0.02), meaning participants entered REM sleep faster
  • Sleep quality deviations also decreased (p < 0.02)

These findings are notable for their size. A 50% increase in deep sleep or REM sleep is a large effect. For context, most pharmaceutical sleep aids improve sleep onset or total sleep time by 10–20% but often suppress deep sleep or REM. MK-677 improved both.

The link between GH and sleep makes biological sense, and this remains one of MK-677's most distinctive findings. For more on peptides and sleep, see our guide to the best peptides for sleep quality.

Study 5: Hip Fracture Recovery — The Trial That Was Stopped Early {#study-5-hip-fracture-recovery-the-trial-that-was-stopped-early}

Adunsky A, Chandler J, Heyden N, et al. "MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study." Archives of Gerontology and Geriatrics. 2011;53(2):183–189.

This is the most important safety study in the MK-677 literature, and it's the reason the FDA lists ibutamoren as posing "significant safety risks due to the potential for congestive heart failure."

The trial enrolled 123 elderly patients recovering from hip fracture surgery. They received 25 mg MK-677 or placebo daily for 24 weeks. The primary endpoint was functional recovery.

Why It Was Stopped Early

Four patients in the MK-677 group (6.5%) developed congestive heart failure during the study, compared to one patient in the placebo group (1.7%). The data safety monitoring board stopped the trial.

The researchers noted that the MK-677 group had higher baseline blood pressures, which could partially explain the imbalance. But in a frail elderly population recovering from hip fracture — exactly the kind of patient who might benefit from GH-mediated recovery — the heart failure signal was concerning enough to halt the study.

Other Results

MeasureMK-677PlaceboSignificance
Stair climbing power+12.5 WBaselinep = 0.292 (not significant)
Gait speed improvement+0.7 scoreBaselinep = 0.011
IGF-1 increase+51.4 ng/mLNo changep < 0.001
Falls during studyFewerMorep = 0.096 (trend)
Total adverse events77% of patients55% of patients—

The gait speed improvement and trend toward fewer falls were positive signals. But 77% adverse event rate vs. 55% in placebo — combined with the heart failure cases — painted a concerning picture for this population.

A separate, similar trial by Bach et al. in 161 elderly hip fracture patients did not report the same heart failure signal. The conflicting results remain unresolved.

Study 6: Body Composition in Obese Males {#study-6-body-composition-in-obese-males}

Svensson J, Lönn L, Jansson JO, et al. "Two-month treatment of obese subjects with the oral growth hormone secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure." Journal of Clinical Endocrinology & Metabolism. 1998;83(2):362–369.

Twenty-four obese men received MK-677 or placebo for two months. The MK-677 group showed increased fat-free mass and a transient rise in basal metabolic rate (BMR). IGF-1 and GH levels both increased.

This study confirmed that MK-677's body composition effects extend to obese populations. But the BMR increase was temporary, fading after the initial treatment period. And as with other studies, the lean mass gains did not translate into measured strength improvements.

Long-Term Benefits: What the Data Supports {#long-term-benefits-what-the-data-supports}

Based on the available clinical trial evidence, MK-677 has demonstrated the following benefits in studies lasting 8 weeks or longer:

BenefitEvidence StrengthDuration StudiedKey Study
Sustained GH and IGF-1 elevationStrongUp to 2 yearsNass et al., 2008
Fat-free mass increase (+1.1 kg)Moderate12 monthsNass et al., 2008
Nitrogen balance preservation during calorie restrictionStrong (small study)7 days of treatmentMurphy et al., 1998
Improved sleep architecture (deep sleep + REM)Moderate7–14 daysCopinschi et al., 1997
Femoral neck BMD increase (with alendronate)Moderate18 monthsMurphy et al., 2001
Gait speed improvement (hip fracture patients)Weak24 weeksAdunsky et al., 2011

The word "moderate" appears often. That's because most studies were small (8–65 participants for the key trials) and the most consistent benefit — GH and IGF-1 elevation — did not reliably translate into functional improvements like strength gains.

Long-Term Risks: What the Data Shows {#long-term-risks-what-the-data-shows}

Insulin Resistance and Blood Glucose

Every long-term MK-677 study that measured glucose metabolism found some degree of impact. Fasting glucose increased by roughly 5 mg/dL on average. Insulin sensitivity declined. HbA1c (a measure of long-term blood sugar control) showed small increases.

A 2023 review described these effects as "very mild" and "not clinically significant" in the Nass trial population. But context matters. In already-metabolically-compromised populations (obese, elderly, prediabetic), even small pushes toward insulin resistance could tip someone into clinical diabetes over months or years of use.

Congestive Heart Failure

The Adunsky hip fracture trial is the only study where heart failure emerged as a safety signal. Four cases in 62 MK-677-treated patients vs. one in 61 placebo patients. The trial was stopped.

Growth hormone is known to cause fluid retention, and the heart is sensitive to volume overload — especially in elderly patients with pre-existing cardiac conditions. The FDA now lists this as a specific risk.

Appetite and Weight Gain

MK-677 activates the ghrelin receptor, and ghrelin drives hunger. Increased appetite is reported in virtually every MK-677 study. For patients who need to eat more (catabolic, wasting conditions), this is a benefit. For others, uncontrolled appetite can lead to unwanted weight gain.

Fluid Retention and Edema

Peripheral edema (swelling, usually in the extremities) appears across studies. It's generally mild and often resolves, but it contributes to the "lean mass" readings on body composition scans and may stress the cardiovascular system in vulnerable populations.

Theoretical Cancer Concern

Chronically elevated IGF-1 is associated with increased cancer risk in epidemiological studies. No MK-677 trial has directly shown increased cancer rates, but the trials have not been long enough or large enough to detect this. The theoretical concern remains — and it is the reason many researchers believe long-term IGF-1 elevation warrants caution.

The Growth Hormone and IGF-1 Question {#the-growth-hormone-and-igf-1-question}

The central promise of MK-677 is restoring youthful GH and IGF-1 levels in aging adults. The Nass trial confirmed it does this effectively, maintaining elevated levels for up to two years without tachyphylaxis.

But a critical question hangs over this result: Is raising GH and IGF-1 in older adults actually beneficial?

The age-related decline in GH (somatopause) may not be purely pathological. Some researchers argue that lower GH and IGF-1 in old age could be protective — slowing cell growth and reducing cancer risk. Studies in centenarians and long-lived animal models often find lower IGF-1 signaling, not higher.

This creates a paradox. In the short term, GH promotes recovery, muscle preservation, and bone health. In the long term, chronically elevated IGF-1 may accelerate aging-related diseases. The two-year Nass trial didn't resolve this — it showed sustained GH elevation without obvious harm, but it wasn't designed or powered to detect cancer, cardiovascular events, or mortality differences.

For related reading on growth hormone secretagogues, see our profiles of CJC-1295 and Ipamorelin, both of which work through the GH axis but via different mechanisms.

Regulatory Status {#regulatory-status}

MK-677 is not FDA-approved for any indication. Key regulatory facts:

  • It remains classified as an Investigational New Drug (IND) in the United States
  • It cannot be legally sold as a dietary supplement or consumer product
  • The FDA has issued warning letters to companies selling products containing MK-677
  • It is on the World Anti-Doping Agency Prohibited List (category S2: Peptide Hormones, Growth Factors, Related Substances)
  • It is on the U.S. Department of Defense Prohibited Dietary Supplement Ingredients List
  • Products marketed online as "MK-677" may contain undisclosed ingredients, wrong dosages, or no active compound at all

The regulatory path forward for MK-677 is unclear. No pharmaceutical company has announced plans for Phase III trials leading to FDA approval.

Frequently Asked Questions {#frequently-asked-questions}

What is the longest MK-677 study in humans? The Nass et al. (2008) trial ran for two years in healthy older adults taking 25 mg daily. It is the only study to follow MK-677 use for this long.

Does MK-677 build actual muscle? MK-677 increases fat-free mass (about 1.1 kg over 12 months in the longest trial), but no study has shown significant improvements in muscle strength or physical function. Some of the mass gain may be intracellular water rather than contractile muscle tissue.

Does MK-677 cause diabetes? MK-677 increases fasting blood glucose and reduces insulin sensitivity in every study that measured these markers. In healthy subjects, these changes have been described as mild. But in people already at risk for type 2 diabetes, the effect could be clinically meaningful over time.

Why was one MK-677 trial stopped early? The Adunsky et al. (2011) trial in elderly hip fracture patients was stopped because 6.5% of MK-677 patients developed congestive heart failure, compared to 1.7% on placebo. The data safety monitoring board judged this an unacceptable risk.

Is MK-677 legal? MK-677 is not FDA-approved and cannot be legally marketed as a supplement or food product in the United States. It can only be used in approved research settings. It is prohibited in competitive sports by WADA.

Does MK-677 improve sleep? Yes. The Copinschi et al. (1997) study found that 25 mg MK-677 increased deep sleep by ~50% and REM sleep by 20–50% in both young and older adults. This is one of the most consistent and largest effects observed in MK-677 research.

Does the growth hormone increase from MK-677 fade over time? No. The two-year Nass trial showed sustained pulsatile GH elevation for the full duration of treatment. Levels returned to baseline after stopping.

How does MK-677 compare to injectable growth hormone? MK-677 raises GH through the body's own pulsatile release mechanism (via ghrelin receptor activation), while injectable GH provides a direct, non-physiological spike. MK-677 is oral; GH requires injection. MK-677 produces lower peak GH levels than therapeutic-dose injections but maintains the natural pulsatile pattern. Neither has been shown to reliably improve strength or function in aging adults.

The Bottom Line {#the-bottom-line}

The clinical trial record for MK-677 tells a consistent story with an uncomfortable tension at its center. The compound works as intended — it raises GH and IGF-1 to youthful levels, and it does so reliably for as long as you take it. Two years of data confirms this.

But raising growth hormone is not the same as improving health outcomes. The strongest functional finding is the reversal of diet-induced catabolism (Murphy et al., 1998). The sleep data is impressive. The bone density data is site-specific and incomplete. And the body composition data consistently shows mass without strength — a finding that raises more questions than it answers.

On the risk side, the insulin resistance signal is small but universal across studies. The heart failure signal from the Adunsky trial — though it came from a frail, elderly population and was not replicated — was serious enough to stop a clinical trial and earn an FDA safety warning.

The honest summary is this: MK-677 is a reliable growth hormone secretagogue with proven short-term metabolic effects, but the long-term risk-benefit ratio remains unknown. No one has studied it for five or ten years. The theoretical cancer risk from chronic IGF-1 elevation has not been tested. And the disconnect between increased lean mass and absent strength gains suggests the anabolic narrative around this compound may be simpler than the biology.

For those interested in peptide-based approaches to recovery and body composition, our peptide stacking guide covers how researchers approach combination strategies with growth hormone secretagogues.

References {#references}

  1. Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008;149(9):601-611. PMC

  2. Murphy MG, Plunkett LM, Gertz BJ, et al. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism. J Clin Endocrinol Metab. 1998;83(2):320-325. PubMed

  3. Murphy MG, Weiss S, McClung M, et al. 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. J Clin Endocrinol Metab. 2001;86(3):1116-1125. PubMed

  4. Copinschi G, Leproult R, Van Onderbergen A, et al. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man. Neuroendocrinology. 1997;66(4):278-286. PubMed

  5. Adunsky A, Chandler J, Heyden N, et al. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011;53(2):183-189. ScienceDirect

  6. Svensson J, Lönn L, Jansson JO, et al. Two-month treatment of obese subjects with the oral growth hormone secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure. J Clin Endocrinol Metab. 1998;83(2):362-369. PubMed

  7. Nass R, Gaylinn BD, Thorner MO. Growth hormone secretagogues as potential therapeutic agents to restore growth hormone secretion in older subjects to those observed in young adults. J Gerontol A Biol Sci Med Sci. 2023;78(Suppl 1):38-42. Oxford Academic

  8. U.S. Department of Defense. Performance Enhancing Substance: MK-677 (Ibutamoren). Operation Supplement Safety. OPSS

  9. DEA/FDA. Beyond the Hype: Potential Health Risks of MK-677. Get Smart About Drugs. 2025. GetSmartAboutDrugs.gov

  10. Healthy Male (Andrology Australia). What you need to know about MK-677 (Ibutamoren). HealthyMale.org.au