A non-peptide, orally active growth hormone secretagogue that mimics ghrelin at the GHS-R1a receptor. Technically not a peptide (it's a small molecule), but included here because it targets the same ghrelin receptor as peptide GH secretagogues and is commonly discussed alongside them. Produces sustained 24-hour GH and IGF-1 elevation from a single oral dose.
MK-677 (ibutamoren mesylate) is a non-peptide, orally active growth hormone secretagogue developed by Merck. While it is not technically a peptide, it is universally discussed alongside peptide GH secretagogues because it targets the same ghrelin receptor (GHS-R1a) and produces similar effects.
MK-677's key advantage over peptide GHRPs is its oral bioavailability — patients take a pill instead of injecting. A single 25mg oral dose produces sustained GH pulsatility and IGF-1 elevation for a full 24 hours, making it the most convenient GH-optimizing compound available.
MK-677 activates the same GHS-R1a receptor as peptide GHRPs but with distinct pharmacokinetics. Its oral bioavailability and sustained receptor occupancy produce continuous GH pulse amplification rather than the single bolus effect of injected peptides. This more closely mimics the physiological GH secretion pattern of a younger individual.
| Pathway | Effect | Significance |
|---|---|---|
| Oral GHS-R1a agonism | Sustained receptor activation from oral dosing | 24-hour GH pulsatility from single daily dose |
| IGF-1 elevation | 40-90% increase in IGF-1 maintained for months | Anabolic, body composition, and recovery effects |
| No desensitization | Unlike hexarelin, IGF-1 elevation maintained for 12+ months | Suitable for long-term use |
| Appetite increase | Moderate ghrelin-mimetic hunger | Less intense than GHRP-6 but more than ipamorelin |
| Sleep improvement | Increases duration of stage 3/4 (deep) NREM sleep | GH is primarily released during slow-wave sleep |
| Study | Design | Findings | Level |
|---|---|---|---|
| IGF-1 elevation | Phase II, n=187, 2 years | 25mg/day increased IGF-1 by ~40% sustained over 2 years with no tachyphylaxis | Level II |
| Body composition | Clinical studies | Increased lean mass (~1.8 kg) and trend toward decreased fat mass over 8 weeks | Level II |
| Bone density | Phase II, elderly | Increased bone mineral density in postmenopausal women after 18 months | Level II |
| Sleep quality | Clinical studies | Increased REM and stage 4 sleep duration by ~50% | Level II |
| Sarcopenia | Phase II, elderly | Improved physical function and lean mass in elderly hip fracture patients | Level II |
Appetite increase: Moderate hunger increase, especially in the first 2-4 weeks. Usually diminishes.
Water retention: Edema, especially in hands and feet. GH-mediated. Usually mild.
Insulin resistance: MK-677 can worsen insulin sensitivity. Fasting glucose and HbA1c should be monitored.
Lethargy: Some users report daytime drowsiness, particularly at higher doses.
Long-term cancer risk: Theoretical concern with chronic GH/IGF-1 elevation. No increased cancer incidence in 2-year studies, but longer-term data is lacking.
| Jurisdiction | Status |
|---|---|
| FDA | Not approved. Merck discontinued development after Phase II. |
| WADA | Banned under S2 (peptide hormones and growth factors — despite being non-peptide, it targets the same pathway) |
| Availability | Widely available as a research chemical. One of the most popular GH-related compounds in biohacking communities. |