GH Secretagogue / Oral / 10-25mg daily (typically at bedtime)
MK-677 (Ibutamoren)
MK-677 was designed at Merck in the early 1990s to do from a tablet what the injected growth-hormone-releasing peptides did, and it became the pharmacological probe used to clone its own receptor three years before anyone found the hormone that receptor was built for. Thirty years of trials raised IGF-1 every time and never produced an approval, so nearly all present-day human use runs through the research-chemical market.
In plain words
MK-677, also called ibutamoren, is a lab-made compound taken by mouth that copies the signal of ghrelin, a hunger hormone, and makes the pituitary gland release growth hormone. It has been through many randomized trials, and they agree on one thing: it reliably raises IGF-1, the blood marker that growth hormone works through. What those trials did not show is benefit. Over twelve months in healthy older adults it added about 1.1 kg of lean mass but did not improve strength or physical function, while fasting blood sugar rose and insulin sensitivity fell; a year-long trial in Alzheimer disease found no effect on thinking or daily function; and a trial in patients recovering from hip fracture was stopped early over a heart failure safety signal, with the investigators calling the safety profile unfavorable in that group. It has never been approved anywhere, it is sold as a research chemical alongside SARMs with no manufacturing or testing standard behind it, it is banned in sport, and an analysis of products bought online found many did not contain what their labels claimed. The trials reported increased appetite, mild fluid retention and muscle pain; users describe the same strong hunger and puffiness, plus numbness in the hands and vivid dreams.
At a glance
| Half-life | 1 days |
|---|---|
| Tmax | 0.042 days |
| Route(s) | Oral |
| Published dosing range | 10-25mg daily (typically at bedtime) |
Reference data from the DosePlot canon -- not a protocol recommendation.
Serum curve
Single 17.5 mg dose by Oral, rendered from the same engine that powers the interactive chart. Relative levels, not lab values.
What does the evidence show?
Two things are labeled separately here because they answer different questions. The tier is how a study was built. The distance chips are whether that study touched this molecule, by this route, in a population resembling the reader. A randomized trial of a different molecule keeps its tier and still says nothing about this compound.
| Finding | Tier | Distance from use | Study |
|---|---|---|---|
| Once-daily oral dosing at 25 mg for two weeks raised mean 24-hour growth hormone concentration by 97 percent, by making existing pulses taller and lifting the troughs between them rather than adding pulses. The trial enrolled 32 healthy adults aged 64 to 81 and split them across placebo and 2, 10 and 25 mg; the 97 percent figure is the 25 mg arm alone. Four weeks at 25 mg moved mean IGF-1 in that arm from 141 to 265 mcg/L, into the normal range for young adults. | rct | not recorded | Chapman IM, et al. Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretagogue (MK-677) in healthy elderly subjects.Journal of Clinical Endocrinology and Metabolism 81(12):4249-4257, 1996 |
| In nine healthy young men, seven days of bedtime dosing at 5 or 25 mg did not increase the total amount of growth hormone secreted over 24 hours. Pulse frequency rose, mostly through extra low-amplitude pulses, and IGF-1 still rose dose-dependently. The drug reshapes the pattern of secretion, and how much it adds depends on how depleted the axis was to begin with. | rct | not recorded | Copinschi G, et al. Effects of a 7-day treatment with a novel, orally active, growth hormone secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men.Journal of Clinical Endocrinology and Metabolism 81(8):2776-2782, 1996 |
| A trial that randomized 65 healthy adults aged 60 to 81 to 25 mg daily or placebo increased fat-free mass in the treated group by 1.1 kg at twelve months, against a 0.5 kg loss in the placebo group, and increased body weight by 2.7 kg against 0.8 kg on placebo. Isokinetic strength and functional measures did not change, and abdominal visceral fat did not fall. | rct | not recorded | Nass R, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.Annals of Internal Medicine 149(9):601-611, 2008 |
| In the treated group of that same 12-month trial, fasting blood glucose rose by an average of 0.3 mmol/L (5 mg/dL) and insulin sensitivity fell. Increased appetite, transient mild lower-extremity edema, and muscle pain were the most frequent side effects, and mean cortisol rose 47 nmol/L. | rct | not recorded | Nass R, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.Annals of Internal Medicine 149(9):601-611, 2008 |
| A trial randomized 563 patients with mild to moderate Alzheimer disease to 25 mg daily or placebo for 12 months, and 416 completed treatment and the 12-month assessments. Serum IGF-1 in the treated patients rose 60.1 percent at six weeks and 72.9 percent at 12 months, with no difference from placebo on any cognitive or functional endpoint. Target engagement was clear; benefit was absent. | rct | not recorded | Sevigny JJ, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.Neurology 71(21):1702-1708, 2008 |
| A phase IIb trial randomized 123 elderly hip-fracture patients, 62 to 25 mg daily and 61 to placebo. IGF-1 in the treated patients rose 51.4 ng/mL over placebo without improving most functional performance measures, and the trial was terminated early because of a congestive heart failure safety signal. The investigators concluded the drug had an unfavorable safety profile in that population. | rct | not recorded | 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.Archives of Gerontology and Geriatrics 53(2):183-189, 2011 |
| In a double-blind placebo-controlled crossover in eight healthy young adults, one week of 25 mg at bedtime increased the duration of stage IV sleep by about 50 percent and REM sleep by more than 20 percent. The older-adult arm of the same paper was uncontrolled and does not support a comparable claim. | rct | not recorded | Copinschi G, et al. Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man.Neuroendocrinology 66(4):278-286, 1997 |
| Community reports track the trial side-effect profile closely: strong hunger within the first few days, water retention and puffy hands, wrist and finger numbness at the top of the range, and vivid dreams. Many users settle at 10 mg, the bottom of the 10 to 25 mg range, which is below the 25 mg dose that produced nearly every published human result. | anecdotal | not recorded | community reports aggregated from reddit, MESO-Rx, and similar forumsno study |
How did it get here?
- preclinical1980-1984
- Cyril Bowers and colleagues report that short synthetic peptides designed from weakly active methionine-enkephalin analogs release growth hormone from rat pituitary tissue. Their 1984 hexapeptide acts directly on the pituitary and produces a growth hormone response with a different time course from the growth-hormone-releasing factors themselves. The earliest indexed papers in this line are from 1980 and 1981; the peptides work, but only by injection, and the receptor they act on is unidentified.
- preclinical1995
- Merck chemists publish MK-0677, a non-peptide built to survive the gut. It releases growth hormone from rat pituitary cells at nanomolar concentrations, is indistinguishable in mechanism from the injected peptides, and works in dogs at low oral doses.
- first-human1996
- The first 24-hour human profiles appear in the same journal months apart: seven days of bedtime dosing in nine healthy young men, and two to four weeks in 32 healthy adults aged 64 to 81 spread across placebo and 2, 10 and 25 mg. In the older cohort's 25 mg arm, growth hormone output nearly doubles. The young group's total output does not rise at all.
- preclinical1996-1999
- The secretagogues are used as the probe to clone their own receptor, which turns out to have no known natural ligand; the paper reporting it concludes that these compounds mimic an undiscovered hormone. Ghrelin is purified from rat stomach three years later. The drug preceded the hormone it imitates.
- clinical-adoption1997-2011
- Merck and its partners run the compound through growth hormone deficiency, obesity, diet-induced catabolism, frailty, Alzheimer disease, and recovery from hip fracture. IGF-1 rises in every trial. Function does not follow, glucose control worsens, and the hip-fracture study stops early over a heart failure signal. The compound is never approved anywhere.
- grey-market2013-2026
- Ibutamoren reaches the public as a research chemical sold beside the SARMs, in capsules, bulk powder, and dropper bottles, none of it made or tested to pharmaceutical standard. The exact year open sale began is not documented, but the World Anti-Doping Agency added growth hormone secretagogues to prohibited-list section S2 in 2013, and ibutamoren is listed there by name under S2.2 today. A 2017 analysis in JAMA of 44 products bought online as SARMs found that only 23 contained a SARM at all, that 17 contained a different unapproved drug, ibutamoren among them, and that the labeled amount of active compound matched the assay in only 18. The molecule itself has been relicensed and remains in pediatric growth-hormone-deficiency trials under a development code.
How is it made?
Production happens in three stages.
1. Building the core. MK-677 is shelved with the peptides and is not one. Its center is a spiro junction: an indoline ring and a piperidine ring sharing a single carbon atom, so the two rings sit at right angles and the molecule holds one rigid shape instead of flexing. Industrial chemistry assembles that cage first, then caps the indoline nitrogen with a methanesulfonyl group.
2. Hanging the side chain. Two amide bonds are formed in sequence onto the piperidine nitrogen, using the coupling chemistry peptide chemists use: first a benzyl-protected serine unit in the D configuration, then a cap built from alpha-methylalanine, whose central carbon carries two methyl groups and no hydrogen. Both choices are the reason this product is swallowed rather than injected. Digestive enzymes that dismantle natural peptides expect L-configured residues and an unobstructed backbone; neither is present here, so the molecule reaches the bloodstream intact.
3. Salt and finish. The free base is converted to its methanesulfonate salt, which crystallizes cleanly and dissolves faster, then recrystallized to strip residual solvent and side products. Regulated manufacture tests each batch for identity, potency, related substances, and residual solvent.
The route is thirty years old and unremarkable. What varies outside regulated manufacture is identity and content rather than the synthesis: the salt weighs more than the drug it carries, nothing requires that testing outside the regulated system, and a research chemical is only as good as the assay nobody ran.
Worth knowing
The acute growth hormone spike shrinks while IGF-1 climbs. Eight volunteers aged 24 to 39 were held at 18 kcal/kg per day for two 14-day periods, taking 25 mg or placebo only during the last seven days of each. Peak serum growth hormone after the first 25 mg dose was 55.9 mcg/L; after a week of daily dosing the peak was 22.6 mcg/L, against placebo peaks of roughly 9 and 7 mcg/L. Mean IGF-1 over the last five treatment days was 264 ng/mL versus 188 ng/mL on placebo, measured after the diet alone had already pulled IGF-1 down from 232 to 186 ng/mL. These are numbers from a calorie-restricted protocol, not from free feeding. The pituitary response to each individual dose partly fades. The sustained signal is IGF-1, not the pulse.
Murphy MG, et al. MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism.Journal of Clinical Endocrinology and Metabolism 83(2):320-325, 1998
The drug arrived before the hormone. The synthetic secretagogues were the pharmacological probe used to clone their own receptor in the pituitary and hypothalamus, and the 1996 paper reporting that work concluded the compounds mimic an undiscovered hormone. Ghrelin was purified from rat stomach three years later, which makes MK-677 one of the few drugs whose receptor was found by the drug and whose natural ligand was found last.
Howard AD, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release.Science 273(5277):974-977, 1996
Milligrams of powder are not milligrams of drug. MK-677 is dosed as the methanesulfonate salt, which carries the counter-ion's mass: ibutamoren free base is 528.7 g/mol by formula C27H36N4O5S, ibutamoren mesylate is 624.8 g/mol by formula C28H40N4O8S2. Twenty-five milligrams weighed out as the salt is about 21 mg of the drug, a gap wide enough to matter across a 10 to 25 mg range.
National Center for Biotechnology Information. PubChem Compound Summary records for ibutamoren (CID 178024) and ibutamoren mesylate (CID 6450830).PubChem chemical database record, National Library of Medicine, retrieved 2026
Written and reviewed by Evan Marlow, developer of DosePlot · Updated 2026-08-27
Not medical advice. DosePlot is an informational tool, not a healthcare provider, and using it creates no provider-patient relationship. Do not start, stop, or change any protocol without the approval of a licensed healthcare professional.
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