MK-677: The Oral Growth Hormone Pill That Changed the Field | Research

The takeaway

MK-0677 was characterized as the most potent orally active GH secretagogue with EC50 of 1.3 nM and confirmed anabolic effects in animals.

EC50 = 1.3 nM
MK-677 releases growth hormone at extremely low concentrations, making it the most potent oral GH secretagogue

What the researchers found

MK-0677 was characterized as the most potent orally active GH secretagogue, with EC50 of 1.3 nM in vitro, oral efficacy in dogs at 0.125 mg/kg, and confirmed anabolic effects in rodents.

Why it matters

MK-0677 became the most widely studied and used oral GH secretagogue. This paper established its potency, oral bioavailability, and anabolic potential, which are the properties that made it a game-changer in the field.

How the study worked

In vitro GH release from rat pituitary cells. Oral dosing studies in dogs measuring GH response. Repeated dosing for 4 days. Rodent anabolic efficacy studies with daily oral dosing.

What this study cannot tell us

Animal study (rat cells, dogs, rodents). Clinical trials later revealed more nuanced effects in humans including increased appetite, blood sugar changes, and water retention.

How to read the evidence

Strong — comprehensive characterization across in vitro, oral dog studies, and rodent anabolic models with dose-response data.

When this study was published

Published in 1995. This foundational paper launched decades of MK-677 research. Subsequent human clinical trials confirmed oral GH-releasing activity but revealed side effects including appetite stimulation and insulin resistance.

The bigger picture

MK-677 became arguably the most important oral GH secretagogue ever developed. It opened the door to replacing GH injections with pills for certain conditions and became widely studied for age-related muscle loss, bone density, and sleep quality.

Questions still open

How do the animal anabolic effects translate to human muscle and bone outcomes with long-term use?
Can the appetite-stimulating and blood sugar effects be separated from the GH-releasing benefits?

Common questions

What is MK-677?

MK-677 (also called ibutamoren) is a small molecule that stimulates the body to release its own growth hormone when taken by mouth. It works by mimicking ghrelin at the growth hormone secretagogue receptor.

How is MK-677 different from growth hormone injections?

MK-677 stimulates your body's own GH release in a pulsatile pattern (more natural), can be taken as a pill, and is much less expensive. GH injections deliver a fixed dose of synthetic hormone directly.

Read the original research

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

Proceedings of the National Academy of Sciences of the United States of America, 92(15), 7001-5

View on PubMed ↗

Citation

Patchett, A A; Nargund, R P; Tata, J R; Chen, M H; Barakat, K J; Johnston, D B; Cheng, K; Chan, W W; Butler, B; Hickey, G. (1995). Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.. Proceedings of the National Academy of Sciences of the United States of America, 92(15), 7001-5.