MK-677 (ibutamoren)

MK-677 (ibutamoren) is an orally active small-molecule agonist of the ghrelin receptor that raises growth hormone and IGF-1 levels. It is not a peptide, and it is not approved for any use.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

MK-677, also known as ibutamoren, is often grouped with growth hormone-releasing peptides because it acts on the same receptor, but it is not a peptide. It is a non-peptide small molecule with a spiropiperidine core, developed by Merck in the 1990s as an orally active growth hormone secretagogue. Unlike the injectable peptide secretagogues, it is absorbed when taken by mouth and has a long duration of action, which in human studies produced sustained increases in growth hormone and insulin-like growth factor 1 (IGF-1).

Clinical studies examined MK-677 in healthy older adults, in people with growth hormone deficiency, after hip fracture, in obesity and in Alzheimer's disease. Some studies reported increases in IGF-1 and lean mass, while others found no benefit on primary clinical outcomes. Reported adverse effects included increased appetite, fluid retention and reduced insulin sensitivity. It was not approved, and it is included here because it is frequently discussed alongside peptide secretagogues.

Compare: Ipamorelin vs MK-677.

Structure

MK-677 is a synthetic small molecule rather than an amino acid chain. Its structure contains a spiro[indoline-3,4'-piperidine] scaffold bearing a methanesulfonyl group, linked to an amino acid-derived side chain that includes an α-aminoisobutyric acid unit and a benzyloxy-substituted moiety. Although it incorporates amino acid-like fragments, it has no peptide backbone in the usual sense. It has been developed and studied mainly as the mesylate (methanesulfonate) salt.

Mechanism

MK-677 is an agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), the receptor for the hormone ghrelin. Activation in the pituitary and hypothalamus increases pulsatile growth hormone secretion, which in turn raises circulating IGF-1. In human studies it also increased appetite, consistent with ghrelin receptor activity in feeding centers.

Because it is orally active and long-acting, MK-677 produces a more sustained elevation of the growth hormone and IGF-1 axis than short-acting peptide secretagogues. Effects on glucose metabolism, including increases in fasting glucose and reduced insulin sensitivity, were reported in clinical studies.

Research

Older adults and body composition

Randomized trials in healthy older adults examined whether MK-677 could restore growth hormone and IGF-1 levels toward those seen in younger people. A two-year randomized trial published in 2008 reported increases in IGF-1 and fat-free mass compared with placebo, without significant changes in strength or function, and noted increases in fasting glucose and reduced insulin sensitivity. These studies are among the most detailed of any oral secretagogue.

Alzheimer's disease

A multicenter randomized trial evaluated MK-677 in people with mild to moderate Alzheimer's disease over twelve months. Despite raising IGF-1, it did not slow disease progression compared with placebo. This negative result is often cited in discussions of the growth hormone axis and neurodegeneration. The trial measured cognitive and global outcomes using standard Alzheimer's disease rating scales. Safety and tolerability findings were broadly in line with other MK-677 studies.

Hip fracture and other populations

Studies examined MK-677 in older adults recovering from hip fracture, in obese adults and in people with growth hormone deficiency. Some reported changes in IGF-1, nitrogen balance or body composition, while effects on functional recovery were limited or inconclusive. A hip fracture study was reported to have been stopped early after a safety signal related to congestive heart failure. These findings contributed to the decision not to pursue approval.

Evidence quality

MK-677 has more human data than most compounds discussed in growth hormone secretagogue research, including randomized phase 2 trials. The data show consistent effects on growth hormone and IGF-1 but no established clinical benefit, alongside metabolic and fluid-related adverse effects. It remains an investigational compound and a reference tool for ghrelin receptor pharmacology. Adverse effects observed across studies included increased appetite, edema and changes in glucose handling.

Regulatory status

MK-677 (ibutamoren) is not approved by the FDA for any use, and it is not a recognized substance for US pharmacy compounding. It is not a peptide, so peptide-specific regulatory discussions do not necessarily apply to it. WADA prohibits ghrelin mimetics and growth hormone secretagogues, including MK-677, at all times under class S2.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

Because MK-677 is a small molecule, the certificate of analysis should confirm identity by mass spectrometry with the expected mass for the free base and specify the salt form, usually mesylate, since the salt changes the mass of active compound per gram of powder. Identity is best supported by NMR or comparison with a reference standard in addition to MS. Purity should be reported by HPLC with UV detection. MK-677 has a defined stereocenter, so enantiomeric purity is relevant and requires a chiral method. Residual solvents and elemental impurities typical of small-molecule synthesis should also be considered.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store MK-677 as a dry solid in a tightly sealed container, protected from light and moisture; room temperature or refrigeration is generally adequate for a crystalline small-molecule salt, with -20 °C preferred for long-term reference material. Solutions in DMSO or other solvents for lab use should be aliquoted and stored at -20 °C or below. Stability data from the specific supplier and the material's documentation should take precedence over general guidance.

Download the MK-677 (ibutamoren) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Ipamorelin

  Ipamorelin is a synthetic pentapeptide growth hormone secretagogue that acts as a selective agonist of the ghrelin receptor (GHS-R1a). It is investigational and not approved for any use.

• GHRP-2

  GHRP-2 (pralmorelin) is a synthetic hexapeptide that stimulates growth hormone release by activating the ghrelin receptor. It has been studied in human endocrine testing and is not approved by the FDA.

• Hexarelin

  Hexarelin is a synthetic hexapeptide growth hormone secretagogue that activates the ghrelin receptor. It has been studied in small human studies of growth hormone release and in cardiovascular research, and is not approved for any use.

• Tesamorelin

  Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.

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. Find on PubMed
2. PubMed: all indexed literature on MK-677 (ibutamoren)
3. ClinicalTrials.gov: registered studies mentioning MK-677 (ibutamoren)