Small Molecule Drug
Ibutamoren (MK-677)
Ibutamoren is an orally active, non-peptide ghrelin receptor agonist that raises growth hormone and IGF-1. Despite being marketed alongside peptides — and frequently mislabelled a SARM — it is a small molecule, it has never been approved for any indication, and FDA lists it in Category 2 of bulk substances that may present significant safety risks.
In depth
How it works
Ibutamoren is a non-peptide small molecule that binds the growth hormone secretagogue receptor (GHS-R1a) — the same receptor the hunger hormone ghrelin acts on. Activating it prompts the pituitary to release its own growth hormone, which in turn raises IGF-1 from the liver.
Two things follow from that mechanism. Because it works through the body's own axis rather than supplying growth hormone directly, its effect is bounded by what the pituitary can produce. And because the receptor it targets is the ghrelin receptor, a sharp increase in appetite is not a side effect of ibutamoren so much as an inseparable feature of it.
It is orally active, unlike the injectable peptide secretagogues it is usually grouped with. That convenience is the main reason it is popular, and it is also why it is frequently and incorrectly sold as a SARM. It is not a SARM: it does not touch the androgen receptor.
What the research shows
Ibutamoren is unusually well studied for a compound sold as a research chemical — and the trials are considerably less flattering than the marketing that cites them. In a two-year randomized, double-blind, placebo-controlled trial in 65 healthy adults aged 60 to 81, 25 mg daily raised growth hormone and IGF-1 into the range of healthy young adults, and increased fat-free mass by 1.1 kg while the placebo group lost 0.5 kg.
The finding that matters most is what did not happen. The increase in fat-free mass produced no measurable improvement in strength or physical function. Meanwhile fasting blood glucose rose by about 5 mg/dL, insulin sensitivity fell, and cortisol increased. In other words, the biomarkers moved impressively and the outcomes people actually want did not follow.
The safety record is worse than the biomarker record suggests. A phase IIb trial of 123 elderly patients recovering from hip fracture was terminated early after a congestive heart failure signal, and its authors concluded that ibutamoren "has an unfavorable safety profile in this patient population." An earlier hip-fracture trial found an 84% rise in IGF-1 with no significant functional benefit. Merck developed the compound and never brought it to approval for any indication.
Safety and who should avoid it
The reduction in insulin sensitivity and rise in fasting glucose are consistent, mechanistically expected consequences of sustained growth hormone elevation, and they make ibutamoren a poor fit for anyone with diabetes or impaired glucose tolerance. The fluid retention that produces mild ankle edema in healthy users is the same physiology implicated in the heart failure signal that stopped the hip-fracture trial.
IGF-1 is a growth signal. Chronically elevating it in the presence of an existing or suspected malignancy is the principal theoretical long-term concern with every compound in this class, and it is why baseline and periodic bloodwork is the single most useful habit available to anyone using one.
Ibutamoren also sits on FDA's Category 2 list of bulk drug substances that may present significant safety risks, which means it is not eligible for compounding under the interim policies. Separately, growth hormone secretagogues are prohibited at all times under the WADA code — in and out of competition — so any athlete subject to anti-doping testing should treat this compound as disqualifying.
Detail
Overview
Ibutamoren is an orally active, non-peptide ghrelin receptor agonist that raises growth hormone and IGF-1. Despite being marketed alongside peptides — and frequently mislabelled a SARM — it is a small molecule, it has never been approved for any indication, and FDA lists it in Category 2 of bulk substances that may present significant safety risks.
Benefits, side effects, and protocols
Benefits list
- Raised growth hormone and IGF-1 into the young-adult range in healthy older adults over 12 months
- Increased fat-free mass by 1.1 kg versus a 0.5 kg loss on placebo at 12 months
- Orally active, so no injection or reconstitution is required
- Increased appetite, which is a benefit only where weight gain is the goal
Side effects
- Increased appetite
- Transient mild lower-extremity edema
- Muscle pain
- Raised fasting blood glucose by about 5 mg/dL and decreased insulin sensitivity
- Increased cortisol
- Congestive heart failure signal that ended a phase IIb trial early in elderly hip-fracture patients
Vendor protocol
- None listed
Clinical protocol
- 25 mg orally once daily — the dose used in the published randomized trials
Evidence
- Moderate
- Unusually well studied for a compound sold as a research chemical, and the trials are not the endorsement they are marketed as. A 2-year randomized controlled trial in 65 healthy older adults raised GH and IGF-1 to young-adult levels and increased fat-free mass, but that gain produced no improvement in strength or function, while fasting glucose rose and insulin sensitivity fell. A separate phase IIb trial in elderly hip-fracture patients was terminated early after a congestive heart failure safety signal, and its authors concluded the compound had an unfavorable safety profile in that population. Merck never brought it to approval.
Regulatory
- Not Fda Approved
Research
Mechanisms
Evidence notes
- Moderate
- Unusually well studied for a compound sold as a research chemical, and the trials are not the endorsement they are marketed as. A 2-year randomized controlled trial in 65 healthy older adults raised GH and IGF-1 to young-adult levels and increased fat-free mass, but that gain produced no improvement in strength or function, while fasting glucose rose and insulin sensitivity fell. A separate phase IIb trial in elderly hip-fracture patients was terminated early after a congestive heart failure safety signal, and its authors concluded the compound had an unfavorable safety profile in that population. Merck never brought it to approval.
Administration
Research links
- 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
- Adunsky A, et al. MK-0677 for patients recovering from hip fracture: phase IIb study terminated early for a congestive heart failure signal. Arch Gerontol Geriatr. 2011
- Bach MA, et al. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. 2004
- FDA — Ibutamoren mesylate is listed in Category 2 of bulk substances that may present significant safety risks
- WADA — The Prohibited List (growth hormone secretagogues are prohibited at all times)
- 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
- Adunsky A, et al. MK-0677 (ibutamoren mesylate) for patients recovering from hip fracture: a phase IIb study terminated early for a congestive heart failure signal. Arch Gerontol Geriatr. 2011
- Bach MA, et al. The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture. J Am Geriatr Soc. 2004
Contraindications
- Diabetes or impaired glucose tolerance, given the reduction in insulin sensitivity
- Heart failure or known cardiac dysfunction
- Active or suspected malignancy, since IGF-1 is a growth signal
- Athletes bound by anti-doping codes: growth hormone secretagogues are prohibited at all times
Components
- None listed
Regulatory data
- Not Fda Approved
Aliases
- MK-677
- MK677
- MK-0677
- Ibutamoren mesylate
- Nutrobal
Related compounds
Half-life
How long does Ibutamoren (MK-677) stay in your system?
No human pharmacokinetic study of this compound has been published, so no half-life can honestly be stated. Here is why.
Guides that cover Ibutamoren (MK-677)
BPC-157, TB-500, CJC-1295 and ipamorelin: what the FDA has actually published about each, why “removed from Category 2” does not mean cleared, and what is still unlawful to compound.
CJC-1295, ipamorelin and MK-677 reliably raise growth hormone and IGF-1 in humans. What the trials have not shown is that raising those numbers produces the outcomes people take them for.
Anti-doping panels detect peptide hormones and secretagogues; standard workplace panels generally do not screen for them. Legality, detectability, and prohibition are three separate questions.
Terminology on this page
Concepts from the glossary that come up around Ibutamoren (MK-677).
A substance that causes a gland to secrete a hormone the body already makes, rather than supplying the hormone directly.
A compound that mimics ghrelin, the hunger hormone, at its receptor — usually to trigger growth hormone release.
A selective androgen receptor modulator — a class that acts on the androgen receptor, and which MK-677 is routinely and wrongly lumped into.
Insulin-like growth factor 1 — the hormone, made largely by the liver in response to growth hormone, that mediates most of growth hormone’s effects.
Frequently asked questions
Is MK-677 a SARM?
No, and this is the most common misconception about it. SARMs act on the androgen receptor. Ibutamoren is a ghrelin receptor agonist that stimulates growth hormone release, and it is not even a peptide — it is an orally active non-peptide small molecule. It is grouped with SARMs by retailers, not by pharmacology.
Is MK-677 legal?
It has never been approved for any indication by the FDA, and it appears in Category 2 of FDA's bulk drug substances list, meaning it may present significant safety risks and is not eligible for compounding. It is sold as a research chemical labelled not for human consumption. It is also prohibited at all times under the WADA anti-doping code.
Does MK-677 build muscle?
It increases fat-free mass. In a two-year randomized trial in healthy older adults, 25 mg daily increased fat-free mass by 1.1 kg relative to placebo. That gain did not translate into any measurable improvement in strength or physical function, and some of the increase in lean mass on growth hormone secretagogues reflects fluid retention rather than contractile tissue.
Does MK-677 cause insulin resistance?
Yes. In the two-year trial, fasting blood glucose rose by roughly 5 mg/dL and insulin sensitivity decreased. This is the expected consequence of sustained growth hormone elevation, and it is why ibutamoren is a poor choice for anyone with diabetes, prediabetes, or impaired glucose tolerance.
Why was an MK-677 trial stopped early?
A phase IIb trial in 123 elderly patients recovering from hip fracture was terminated early because of a congestive heart failure safety signal in a limited number of patients. The investigators concluded that the compound had an unfavorable safety profile in that population. Growth hormone drives fluid retention, which is poorly tolerated by patients with subclinical cardiac dysfunction.
Why does MK-677 make you so hungry?
Because it activates the ghrelin receptor, and ghrelin is the hormone that makes you hungry. The appetite increase is inseparable from the mechanism rather than an incidental side effect. In the two-year trial the effect subsided over a few months for most participants.
Educational reference only. Pepperz does not provide medical advice, diagnosis, treatment, prescribing guidance, or dosing recommendations. Sourcing Ibutamoren (MK-677)? Check your source before you use anything.