MK-677
An oral pill that mimics ghrelin: it raised growth hormone and IGF-1 for up to two years in Merck's trials and added lean mass in older adults, but failed in Alzheimer's disease and hip-fracture recovery and raised blood sugar.
MK-677, or ibutamoren, is a small molecule built in the 1990s to do what GHRP-6 does, by mouth and all day. Merck tested it in more than a thousand people, from older adults and obese men to children with growth hormone deficiency, and it reliably lifted IGF-1. It never became a medicine: its largest trials missed their clinical goals, one was stopped over heart failure, and FDA now lists it among substances with significant safety risks.
What is it?
MK-677 is sold and discussed as a peptide, but it is not one. Merck's chemists designed it in the 1990s as a spiroindoline, a compact drug-like molecule, using the peptide GHRP-6 as their template. The goal was a secretagogue that could be swallowed and would work for a whole day. In dogs a single oral dose raised growth hormone for six hours and IGF-1 for longer, which no peptide in the family did.
In people it kept that promise on the laboratory measures. Once-daily doses of 10 to 25 mg raised the height of growth hormone pulses and brought IGF-1 in older adults into the young-adult range within two to four weeks. Short trials found it reversed the nitrogen loss of a calorie-restricted diet, increased markers of both bone formation and bone breakdown, deepened sleep, and in obese men increased fat-free mass over eight weeks without reducing fat.
The long trials are where it stalled. In 65 healthy older adults a year of 25 mg a day added about 1.1 kg of fat-free mass while placebo lost 0.5 kg, but weight, limb fat and fasting glucose rose and insulin sensitivity fell. In 563 people with mild to moderate Alzheimer's disease it raised IGF-1 by 73% and did nothing for cognition or daily function. In older people recovering from hip fracture two trials found little functional benefit, and the second was stopped early over a signal of congestive heart failure.
Merck did not take it to market. The molecule has since returned as LUM-201 in trials for children with growth hormone deficiency, while the product sold online as MK-677 is an unapproved research chemical. FDA's advisers voted 13 to 1 against allowing it in pharmacy compounding in 2024, FDA lists it among substances with significant safety risks, and in December 2025 FDA warned a company whose children's growth products contained it undeclared.
Mechanism of Action
MK-677 activates the ghrelin receptor, the same target as GHRP-6 and ghrelin itself, but as an oral small molecule with a long action. It amplifies the body's own growth hormone pulses rather than replacing them, which is why IGF-1 rises steadily with daily dosing.
Every step was measured in people, but only for weeks and only in hormones, lean mass and bone markers. Outcomes that matter to patients were not measured.
Each step is tagged with where it was shown. A dashed red arrow marks a link the evidence does not establish.
The pathway in words
- MK-677. An orally active mimic of growth hormone-releasing peptides, taken once a day. Shown in: people. Source: PubMed 8954023.
- More growth hormone pulses. In nine young men over a week, pulses grew more frequent, mostly small ones, and IGF-1 rose with dose; cortisol barely changed. Shown in: people. Source: PubMed 8768828.
- IGF-1 back to young levels. In 32 adults aged 64 to 81, 25 mg daily nearly doubled 24-hour growth hormone and lifted IGF-1 from 141 to 219 µg/L, the young-adult range. Shown in: people. Source: PubMed 8954023.
- More lean mass. In 24 obese men over 8 weeks, IGF-1 rose about 40% and fat-free mass increased; total and visceral fat did not change, and glucose tolerance worsened. Shown in: people. Source: PubMed 9467542.
- Faster bone turnover. In 105 functionally impaired older adults over 9 weeks, bone-formation markers rose (osteocalcin 29.4%) and so did a resorption marker (22.6%). Shown in: people. Source: PubMed 10404019.
- not measured. Stronger bones or muscles. These trials lasted weeks and measured hormones, lean mass and bone markers, not fractures, strength or function. Shown in: people. Source: PubMed 10404019.
Ghrelin receptor: growth hormone pulses
In older adults, 25 mg a day raised mean 24-hour growth hormone by 97% by making existing pulses taller, without adding pulses. In young men the total secreted barely changed but pulse frequency rose. Either way IGF-1 went up steadily.
The response partly fades
In dogs, repeated daily dosing cut the growth hormone response by 41 to 77% while IGF-1 stayed up to 126% above control. In obese men the first dose raised growth hormone and prolactin more than later doses did.
Appetite and blood sugar
Its best-documented side effects follow from ghrelin's own biology: appetite rose early in the year-long trial, and fasting glucose rose while insulin sensitivity fell in older and obese adults.
Cortisol, briefly
Single doses raised cortisol in dogs and briefly in obese men, but 24-hour cortisol did not change in young men or older adults on daily dosing, and in dogs the cortisol response faded with repeated doses.
Published Research
Our evidence set holds 50 papers that name MK-677 or ibutamoren. Twenty-seven name it in their titles and have an abstract; 20 are carded below, chosen to cover every human trial in the set and the animal work that explains it: 17 studies in people and 3 in animals. The pivotal one-year trial in older adults is listed under References without a card because its title calls MK-677 only 'an oral ghrelin mimetic'. Two trials were added to the set by hand. Most of the human data come from the drug's development programme in the 1990s and 2000s.
Single oral doses in beagles
In an eight-dog crossover, single oral doses of 0.25, 0.5 and 1.0 mg/kg raised peak growth hormone 5.3-, 9.0- and 15.8-fold. After 1 mg/kg it stayed elevated for up to 360 minutes, longer than GHRP-6, and IGF-1 rose 30% by 480 minutes. Cortisol rose about 2.4-fold; prolactin and LH did not change.
Older adults, 2 and 4 weeks
Thirty-two healthy adults aged 64 to 81 took placebo or 2, 10 or 25 mg daily. At 25 mg, 24-hour growth hormone rose 97% after two weeks through taller pulses, and IGF-1 rose from 141 to 265 µg/L at four weeks, into the young-adult range. Fasting glucose rose from 5.4 to 6.8 mmol/L; prolactin rose 23% within the normal range and cortisol did not change.
Young men, one week
Nine healthy young men took placebo, 5 mg or 25 mg at bedtime for seven days in a crossover. The amount of growth hormone secreted was similar, but pulse frequency rose with both doses and IGF-1 increased with dose. Apart from a shift in its daily rhythm, cortisol, including 24-hour free cortisol, was unchanged.
Repeated doses in beagles
The first oral dose raised growth hormone 3.9- to 9.8-fold depending on dose; with daily repetition the response fell by 41 to 77% but stayed above control at the higher doses. IGF-1 rose up to 126% and stayed up for the 14-day study with daily, but not alternate-day, dosing, and the cortisol response faded with daily dosing.
Sleep
In eight young adults, 25 mg at bedtime for seven days lengthened stage 4 sleep by about 50% and REM sleep by more than 20% against placebo, and deviations from normal sleep fell from 42% to 8%. In six adults aged 65 to 71, 14 days of treatment increased REM sleep by nearly 50% and shortened REM latency.
Diet-induced protein loss
Eight healthy volunteers on 18 kcal/kg a day for two 14-day periods took 25 mg or placebo in the second week. Nitrogen balance was +0.31 g/day on MK-677 against −1.48 on placebo, and IGF-1 rose to 264 ng/mL against 188. The growth hormone peak fell from 55.9 µg/L after the first dose to 22.6 after a week.
Obese men, 8 weeks: body composition
Twenty-four obese men took 25 mg or placebo daily for eight weeks. IGF-1 rose about 40% and fat-free mass increased significantly, while total and visceral fat did not change. Basal metabolic rate rose at two weeks but not significantly at eight. Fasting glucose and insulin were unchanged, but glucose tolerance tests showed impairment at two and eight weeks.
Obese men, 8 weeks: bone markers
In the same design, markers of bone formation rose within two weeks (type I procollagen peptide +23%, type III +28%) and osteocalcin by 15% at eight weeks, while resorption markers also rose (telopeptide +26%, urinary calcium/creatinine +46%). IGFBP-5 rose 43 to 44%. Whether bone mass would increase was left to longer studies.
Bone turnover in older adults, 187 people
Across three placebo-controlled trials lasting 2 to 9 weeks in adults aged 65 or older, MK-677 raised IGF-1 by 55 to 94% and increased bone turnover. In 105 functionally impaired elderly people given up to 25 mg daily for nine weeks, osteocalcin rose 29.4%, bone alkaline phosphatase 10.4% and urinary NTX 22.6% against placebo.
Children with growth hormone deficiency
Eighteen prepubertal children with idiopathic growth hormone deficiency took 0.2 or 0.8 mg/kg a day for 7 to 8 days. At 0.8 mg/kg the median growth hormone peak rose by 3.8 µg/L and IGF-1 by 12 µg/L, with wide ranges, and prolactin, glucose, thyroid hormones, cortisol and insulin did not change.
Postmenopausal osteoporosis, 292 women
Women aged 64 to 85 with low bone density took MK-677 25 mg, alendronate 10 mg, both or placebo. MK-677 raised IGF-1 by 39 to 45% and bone turnover markers, partly offset alendronate's suppression of bone formation, and with alendronate raised femoral-neck density more than alendronate alone (4.2% vs 2.5%); the gain was not seen at other sites.
Hip fracture recovery, 161 patients
Previously mobile patients aged 65 or older took MK-0677 or placebo for six months after hip fracture at 13 centres. IGF-1 rose 84% against 17% on placebo, but there were no significant differences in functional performance or overall disability scores; trends toward benefit in some leg measures did not reach significance.
Alzheimer's disease, 563 patients
People with mild to moderate Alzheimer's disease took 25 mg or placebo daily for 12 months, and 416 completed. IGF-1 rose 60.1% at six weeks and 72.9% at a year, but there were no differences on the clinician's global impression, the ADAS-Cog cognitive scale, daily-living activities or dementia rating. The authors concluded it did not slow progression despite target engagement.
Hip fracture, stopped for heart failure
In 123 older hip-fracture patients given 25 mg or placebo, IGF-1 rose by 51.4 ng/mL, gait speed improved modestly at 24 weeks and falls were fewer, but stair-climbing power and other functional measures did not improve. The trial was terminated early because of a congestive heart failure signal in a limited number of patients, and the authors called the safety profile unfavourable in this population.
Hemodialysis patients, 3 months
In a randomised crossover, 22 of 26 hemodialysis patients completed three months of MK-0677 and placebo. IGF-1 rose 1.76-fold on the drug against no change on placebo, a 65% greater increase after adjustment, with no serious adverse effects attributed to MK-0677. Whether that helps protein-energy wasting was left to longer trials.
Alzheimer's model mice
In 5xFAD mice treated before symptoms, MK0677 increased the birth of new hippocampal neurons but did not prevent amyloid build-up, synapse loss, microglial activation or cognitive decline, and at 3 mg/kg it significantly increased mortality. Together with the failed human trial, the authors judged it ineffective alone for Alzheimer's disease.
LUM-201: who responds
An analysis of a completed randomised trial in 68 untreated prepubertal children with growth hormone deficiency looked for markers of response to oral LUM-201, the same molecule, against daily growth hormone injections. A baseline IGF-1 above 30 ng/mL and a growth hormone peak of at least 5 ng/mL after one dose picked out children who grew better on LUM-201; the rest did better on injected growth hormone.
Case study: with a SARM
A 25-year-old man took LGD-4033 10 mg and MK-677 15 mg daily for five weeks. Lean mass rose 3.1% and fat mass 15.4%, while bone density fell 2.1%, triglycerides rose 39%, LDL 40%, HDL fell 36%, ALT rose 205% and total testosterone fell 62%. One person on two drugs, so the effects cannot be assigned to MK-677.
Case report: liver injury
An otherwise healthy man in his early 30s developed raised liver enzymes after two months of MK-677 bought as a performance supplement. His liver tests returned to normal after he stopped. The authors note oedema, increased appetite and muscle pain as its known side effects and liver injury as rarely reported.
Detection in hair
After a single 10 mg dose in a volunteer, ibutamoren was detectable in hair four weeks later at 1.3 pg/mg; hair from a person who took sixty 10 mg capsules over 90 days for athletic performance contained 224 pg/mg. The authors present these as reference points for interpreting hair tests in anti-doping cases.
What people say, and what was measured
MK-677 is unusual on this site: it was tested properly, in large trials, by the company that developed it, and then abandoned. That makes the gap between claim and evidence easy to state, because the trials measured exactly the things people claim.
It builds muscle, because it raises growth hormone and IGF-1 the way injected growth hormone does.
Heard in: Experimental Physiology, LGD-4033 and MK-677 use impacts body composition, circulating biomarkers and skeletal muscle androgenic hormone concentrations, which records that these compounds are increasingly used among recreationally active people (read October 1, 2026). Source
The hormone rise is real and repeatedly measured: daily oral MK-677 raised growth hormone and IGF-1 in healthy adults and kept them raised with repeated dosing. The two-year trial in 65 healthy older adults then measured what that produced: fat-free mass increased, and the increase did not translate into any change in strength or function. PMID: 8954023, 9071975, 18981485
Tested in people; mixedIt strengthens bone and helps recovery from fracture.
Heard in: Grey Peptides listing review, October 1, 2026: listings present MK-677 as improving bone density and recovery. Sellers are not named.
Markers of bone formation and turnover rose in treated adults, and bone density changes consistent with increased remodelling were seen in the two-year trial. The trials that measured outcomes rather than markers were less kind: in 123 elderly patients recovering from hip fracture, gait speed improved but several other measures of function did not, and a larger trial found no benefit on the primary measures. PMID: 9661080, 18981485, 21067829, 15066065
Tested in people; mixedIt improves sleep.
Heard in: Journal of Clinical Endocrinology and Metabolism, Prolonged oral treatment with MK-677 improves sleep quality in young and elderly adults, the trial the claim comes from (read October 1, 2026). Source
This claim is one of the few with a trial behind it. A week of treatment changed sleep structure, and prolonged treatment improved sleep quality in both young and elderly adults, measured in a sleep laboratory. It was never developed or approved for sleep, and the trials are small and decades old. PMID: 9349662, 8768828
Tested in people; supportedIt is a safe way to raise growth hormone, with water retention as the only real downside.
Heard in: BMJ Case Reports, Hepatotoxicity induced by MK-677, which records that MK-677 is gaining popularity among performance-enhancing supplements and that its known effects include oedema, increased appetite and muscle pain (read October 1, 2026). Source
The trials found swelling of the lower legs and muscle pain, a rise in cortisol, and in people with Alzheimer's disease a trial of 563 patients found no benefit on progression. Beyond the trials, a 2025 case report describes liver injury in an otherwise healthy man in his early thirties after two months of use, which resolved on stopping. The drug was never approved for anything. PMID: 18981485, 19015485, 40675653
Tested in people; mixedEach claim is quoted from where it is said, never from a seller, and checked as of October 1, 2026 against the studies listed below.
Dosing Data
MK-677 has no approved dose. The trials gave it once a day by mouth, usually 25 mg in adults (range 2 to 50 mg), for anything from one week to two years; children with growth hormone deficiency took 0.2 to 0.8 mg/kg a day for about a week.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
→ Full MK-677 dosage guide — the community figures, the 25 mg trial dose and its blood-sugar and fluid effects, and why a pill is not measured in syringe units
Side Effects & Contraindications
Reported Side Effects
These come from the trials and case reports above, which followed thousands of person-months of dosing.
Contraindications & Cautions
No approved label exists. These cautions follow from what the trials and FDA reported.
Legal Status
MK-677 is not approved as a medicine anywhere. In the United States it cannot be compounded or sold as a supplement.
Frequently Asked Questions
?Is MK-677 a peptide?
No. It is a small-molecule spiroindoline designed to copy what the peptide GHRP-6 does, which is why it works by mouth. It sits in peptide guides because it is sold and stacked alongside peptide secretagogues.
?Does MK-677 build muscle?
In trials it increased fat-free mass: about 1.1 kg over a year in healthy older adults against a 0.5 kg loss on placebo, and significantly over eight weeks in obese men. Strength and function did not improve in the older-adult or hip-fracture trials, and weight and limb fat also rose.
?Why was MK-677 never approved?
The published trials show why it was a hard case: it raised IGF-1 reliably but failed to slow Alzheimer's disease in 563 patients, gave little functional benefit after hip fracture, raised blood sugar, and a hip-fracture trial was stopped over heart failure. Merck did not market it, and it is now being studied again as LUM-201 in children.
?Does MK-677 raise blood sugar?
Yes. At 25 mg a day fasting glucose rose from 5.4 to 6.8 mmol/L in older adults over four weeks, glucose tolerance was impaired in obese men, and in the year-long trial fasting glucose rose and insulin sensitivity fell.
?Does MK-677 improve sleep?
In one small 1997 study, 25 mg at bedtime lengthened deep (stage 4) sleep by about 50% and REM sleep by more than 20% in young adults, and increased REM sleep in older adults. No larger trial has tested sleep.
?Can MK-677 be sold as a supplement or compounded?
Not legally in the United States. FDA has stated that ibutamoren is excluded from the dietary-supplement definition, it is in Category 2 for both 503A and 503B compounding, and FDA's advisers voted 13 to 1 against adding it to the compounding list in 2024.
References
- [Animal] Jacks T, et al. "MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles." Endocrinology, 1996;137(12):5284-9. PMID: 8940347.
- [Human] Chapman IM, et al. "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." J Clin Endocrinol Metab, 1996;81(12):4249-57. PMID: 8954023.
- [Human] Copinschi G, et al. "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." J Clin Endocrinol Metab, 1996;81(8):2776-82. PMID: 8768828.
- [Animal] Hickey GJ, et al. "Repeat administration of the GH secretagogue MK-0677 increases and maintains elevated IGF-I levels in beagles." J Endocrinol, 1997;152(2):183-92. PMID: 9071975.
- [Human] Copinschi G, et al. "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man." Neuroendocrinology, 1997;66(4):278-86. PMID: 9349662.
- [Human] Murphy MG, et al. "MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism." J Clin Endocrinol Metab, 1998;83(2):320-5. PMID: 9467534.
- [Human] Svensson J, et al. "Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure." J Clin Endocrinol Metab, 1998;83(2):362-9. PMID: 9467542.
- [Human] Svensson J, et al. "Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males." J Bone Miner Res, 1998;13(7):1158-66. PMID: 9661080.
- [Human] Murphy MG, et al. "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." J Bone Miner Res, 1999;14(7):1182-8. PMID: 10404019.
- [Human] Codner E, et al. "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." Clin Pharmacol Ther, 2001;70(1):91-8. PMID: 11452249.
- [Human] Murphy MG, 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):1116-25. PMID: 11238495.
- [Human] Bach MA, et al. "The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture." J Am Geriatr Soc, 2004;52(4):516-23. PMID: 15066065.
- [Human] Sevigny JJ, et al. "Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial." Neurology, 2008;71(21):1702-8. PMID: 19015485.
- [Human] Adunsky A, 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):183-9. PMID: 21067829.
- [Human] Campbell GA, et al. "Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study." Nephrol Dial Transplant, 2018;33(3):523-530. PMID: 28340044.
- [Animal] Tian J, et al. "MK0677, a Ghrelin Mimetic, Improves Neurogenesis but Fails to Prevent Hippocampal Lesions in a Mouse Model of Alzheimer's Disease Pathology." J Alzheimers Dis, 2019;72(2):467-478. PMID: 31594237.
- [Human] Bright GM, et al. "Development of a Predictive Enrichment Marker for the Oral GH Secretagogue LUM-201 in Pediatric Growth Hormone Deficiency." J Endocr Soc, 2021;5(6):bvab030. PMID: 33982679.
- [Human] Cardaci TD, et al. "LGD-4033 and MK-677 use impacts body composition, circulating biomarkers, and skeletal muscle androgenic hormone and receptor content: A case report." Exp Physiol, 2022;107(12):1467-1476. PMID: 36303408.
- [Human] Cobani E, et al. "Hepatotoxicity induced by MK-677." BMJ Case Rep, 2025;18(7). PMID: 40675653.
- [Human] Kintz P, et al. "Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue." Clin Chim Acta, 2026;578:120578. PMID: 40882886.
- [pubmed] Nass R, 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):601-11. PMID: 18981485.
- [fda-pi] US FDA. Pharmacy Compounding Advisory Committee meeting, October 29, 2024: summary minutes, Section 503A Bulk Drug Substances List, ibutamoren mesylate (vote: 1 yes, 13 no).
- [fda-pi] US FDA. Warning letter to AgeBox Inc (MARCS-CMS 718252), December 19, 2025: undeclared ibutamoren mesylate found in iKids-Growth products; ibutamoren excluded from the definition of a dietary supplement under FD&C Act section 201(ff)(3)(B)(ii).
Sources & Citations
Every PubMed citation on this page has been checked against its record; two FDA documents, the October 2024 advisory committee minutes and a December 2025 warning letter, were read at fda.gov. The one-year trial in older adults is listed without a card because its title names only an oral ghrelin mimetic. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.