MK-677

Non-peptide ghrelin receptor agonist · Also known as Ibutamoren, Ibutamoren mesylate, Oratrope

What is mk-677?

An orally active growth hormone secretagogue that mimics ghrelin to stimulate sustained GH and IGF-1 release. Technically a non-peptide small molecule, but commonly grouped with GH peptides due to its mechanism.

MK-677 has been studied in several clinical trials, including a 12-month randomized controlled trial in adults aged 60-81 that showed increases in GH and IGF-1 to young-adult levels and gains in fat-free mass. However, it did not improve strength or function in that trial, and some lean mass gains may reflect intracellular water retention. A separate trial in heart failure patients was stopped early due to safety concerns. The FDA has flagged it as posing significant safety risks and it remains unapproved.

Key takeaway: MK-677 is the only oral GH secretagogue with multiple clinical trials, but concerns about blood sugar elevation and potential cardiac risks limit its clinical adoption.

Benefits & evidence

Increased GH and IGF-1 High confidence
Fat-free mass gains Moderate confidence
Improved sleep quality Moderate confidence
Bone mineral density Preliminary confidence
Muscle recovery Preliminary confidence

How it works

MK-677 is a non-peptide agonist of the ghrelin receptor (GHS-R1a). By mimicking ghrelin, it signals the pituitary to release growth hormone in a pulsatile fashion. Unlike injectable GH secretagogues, it is orally bioavailable, which makes it convenient but also means it produces more sustained ghrelin receptor activation.

This sustained activation raises GH and IGF-1 levels over a 24-hour period but also stimulates appetite (a natural ghrelin effect) and can increase fasting glucose and reduce insulin sensitivity. It does not significantly suppress the body's own GH production, and its effects on GH persist for months without tachyphylaxis.

Dosing information

Typical dosing protocol
Starting dose

10 mg/day oral

Weeks 1-2
Maintenance dose

25 mg/day oral

8-12 weeks

Typically taken at night to align GH release with sleep. Appetite increase is most pronounced in the first few weeks. Monitor fasting blood glucose. Consult your healthcare provider.

Side effects

Most side effects tend to improve as your body adjusts.

Increased appetite Common
Water retention and edema Common
Elevated fasting blood glucose Common
Muscle or joint pain Uncommon
Numbness/tingling Uncommon
Reduced insulin sensitivity Uncommon
Congestive heart failure (in at-risk populations) Rare

Research (10 studies)

New directions in growth hormone treatment in children. Pediatric endocrinology, diabetes, and metabolism · 2025