C tier · mixed
It has the longest controlled human exposure of any compound here, a two-year randomised trial with 12-month primary analysis, but the efficacy is confined to fat-free mass with no functional benefit and it carries a concrete cardiac safety signal that ended a trial early.
mk-677
MK-677 is an orally active non-peptide agonist of the ghrelin receptor (GHS-R1a) that raises pulsatile growth hormone and IGF-1 into the young-adult range in older people. It has never been approved anywhere, and a phase 2b hip-fracture trial was terminated early for a congestive heart failure imbalance.
// we supply this one
available as a research reagent
≥ 98% HPLC · research solution · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
MK-677 is a pill rather than an injection, and it works by copying the hunger hormone ghrelin to make the pituitary release growth hormone. It genuinely raises growth hormone and IGF-1 for months at a time, but it also makes people more insulin resistant and one trial in frail elderly patients was stopped early because of heart failure cases.
regulatory status
Not approved; rejected for compounding
Never approved by FDA for any indication, prohibited by WADA and on the DoD Prohibited Dietary Supplement Ingredients List; the Pharmacy Compounding Advisory Committee voted 1 yes / 13 no against including ibutamoren mesylate on the 503A Bulks List on 29 October 2024, citing fluid retention, congestive heart failure and hyperglycaemia.
how it works · proposed mechanism
MK-677 hijacks the hunger-hormone receptor to drive growth hormone release, which explains both its effects and its side effects.
Copies ghrelin at GHS-R1a
MK-677 is a non-peptide agonist at the growth hormone secretagogue receptor 1a, the same receptor endogenous ghrelin uses. Activation on pituitary somatotrophs triggers GH release through a Gq/phospholipase C pathway distinct from the cAMP pathway used by GHRH.
Amplifies existing pulses
Chapman 1996 measured 24-hour GH profiles and found MK-677 raised pulse height and interpulse nadir concentrations without changing the number of pulses. The pulsatile architecture of GH release is preserved rather than overwritten.
Appetite is an on-target effect
GHS-R1a is the receptor that mediates ghrelin's hunger signal in the hypothalamus, so increased appetite is not a side reaction but the same receptor doing its other job. Nass 2008 reported appetite increase as the most frequent adverse effect, subsiding over months.
Insulin sensitivity falls
Growth hormone is directly counter-regulatory to insulin, so sustained GH elevation reduces peripheral glucose disposal. Nass 2008 measured a fasting glucose rise of 0.3 mmol/L and a decline in insulin sensitivity over 12 months.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The Adunsky 2011 phase 2b hip-fracture trial in 123 patients aged 60 and over was terminated early for a congestive heart failure safety signal, with 4 cases (6.5%) on MK-677 versus 1 (1.7%) on placebo, and FDA cites this alongside fluid retention and hyperglycaemia as the basis for rejecting it for compounding. Separately, Nass 2008 showed fasting glucose rose 0.3 mmol/L and insulin sensitivity fell over 12 months, and the fat-free mass gain of 1.1 kg came with no improvement in strength or function.
key published findings
- Human RCT (Nass, Annals of Internal Medicine 2008, n=65 healthy adults aged 60-81): 25 mg oral MK-677 daily for 2 years with 12-month primary analysis raised GH and IGF-1 to young-adult levels and increased fat-free mass by 1.1 kg versus a 0.5 kg decrease on placebo (p<0.001), with no significant difference in abdominal visceral fat; fasting glucose rose 0.3 mmol/L (p=0.015), insulin sensitivity declined and cortisol rose 47 nmol/L (p=0.020).
- Human RCT (Adunsky, Archives of Gerontology and Geriatrics 2011, n=123 patients aged ≥60 recovering from hip fracture): 24-week randomised placebo-controlled phase 2b terminated early for a congestive heart failure safety signal, with 4 CHF cases (6.5%) on treatment versus 1 (1.7%) on placebo.
- Human RCT (Chapman, JCEM 1996, n=32 healthy subjects aged 64-81): 25 mg/day for 2 weeks increased mean 24-h GH concentration by 97 ± 23% by enhancing pre-existing pulsatile secretion, restored IGF-1 into the young-adult range (141 → 265 µg/L at 4 weeks), and significantly raised fasting glucose from 5.4 to 6.8 mmol/L (p<0.01); cortisol was unchanged and prolactin rose 23% but stayed within normal range.
- Human RCT (Chapman, JCEM 1997, n=9 severely GH-deficient men aged 17-34): 10 and 50 mg/day for 4 days raised IGF-1 by 52% and 79% respectively, but the GH response was greatest in subjects who were least deficient at baseline, and fasting and postprandial insulin rose significantly.
- Human RCT (Sevigny 2008, n=563 with mild-to-moderate Alzheimer's disease): 12-month randomised trial reviewed by FDA; the agency concluded the ibutamoren evidence base provides insufficient data to establish effectiveness for any proposed indication.
limitations of the evidence
- No trial has demonstrated a functional benefit; the fat-free mass gain in Nass 2008 was not accompanied by improvements in strength, gait speed or physical performance.
- Published human pharmacokinetic characterisation is thin, and FDA's 2024 review noted missing data on chiral purity, drug substance impurities and residual solvents.
- The congestive heart failure imbalance came from a single 123-patient trial in a frail post-fracture population, so its relevance to healthy users is unresolved rather than settled either way.
identity
| full name | Ibutamoren mesylate, a non-peptide growth hormone secretagogue receptor agonist |
| category | Growth Hormone |
| modality | small molecule |
| formula | C27H36N4O5S |
| molar mass | 528.66 g/mol |
| cas | 159634-47-6 |
| half-life | Not well characterised in published human PK; once-daily oral dosing sustains 24-h GH and IGF-1 elevation |
laboratory handling
| storage | Ibutamoren mesylate powder is stable for approximately 4 years at -20°C per FDA's review; laboratory stocks are kept desiccated, sealed and protected from light and moisture. Aqueous or DMSO stock solutions are aliquoted and frozen at -20°C or below to avoid freeze-thaw cycles. |
| solubility | Unlike the peptides in this class MK-677 is a small molecule with high aqueous solubility, reported at 92 mg/mL in both water and ethanol; DMSO is the usual solvent for concentrated laboratory stock solutions. |
| co-studied with | MK-677 is a GHS-R1a agonist and is co-studied with GHRH-receptor agonists on the same complementary-receptor rationale used for injectable GHRPs, but no published controlled trial has combined MK-677 with a GHRH analogue. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedU.S. Food and Drug Administration · 2024 · official
U.S. Food and Drug Administration · 2024 · official
Annals of Internal Medicine · 2008 · peer-reviewed
Archives of Gerontology and Geriatrics · 2011 · peer-reviewed
Journal of Clinical Endocrinology & Metabolism · 1996 · peer-reviewed
Operation Supplement Safety, U.S. Department of Defense · 2024 · review
others in Growth Hormone