Discontinued Growth Hormone Axis

MK-677

also known as: Ibutamoren, Ibutamoren mesylate, MK-0677, MK0677, LUM-201, Nutrobal

An orally active non-peptide ghrelin receptor agonist — included here by convention because it is universally marketed alongside peptide GH secretagogues. FDA warns of heart failure risk.

A small-molecule GHS-R1a agonist originally developed by Merck for osteoporosis and frailty, with sustained 24-hour GH-axis elevation after a single oral dose — discontinued from development after Phase 3 safety signals.

Mechanism of action

Non-peptide agonist at GHS-R1a (ghrelin receptor), mimicking endogenous ghrelin. Stimulates pulsatile GH release from anterior pituitary somatotrophs, elevates IGF-1, and activates hypothalamic AgRP/NPY neurons producing appetite stimulation. Unlike peptide GHRPs, MK-677 is orally active and has a 24-hour functional duration.

Primary uses

Pediatric GH deficiency (LUM-201 investigational)
GH-axis research
Community use for GH/IGF-1 elevation (not FDA-approved)

Typical dosing

10–25 mg once daily (oral)

Community dosing. FDA has issued warning letters against consumer sales. Elevated appetite, water retention, and insulin resistance are common.

→ Full MK-677 dosage guide — oral 10–25 mg/day ranges, what the human trials actually showed, timing and half-life, the heart-failure safety signal, and regulatory context.

Regulatory status

Not approved. Merck discontinued development after a Phase 3 trial in older adults was halted early over concerns about congestive heart failure incidence. FDA has issued warning letters to companies selling MK-677 in consumer products. Banned by WADA under S2 (Peptide Hormones & Growth Factors) despite being a small molecule. LUM-201 (the same molecule under a new sponsor, Lumos Pharma) is in clinical trials for pediatric GH deficiency.

References

[fda-pi] US FDA. "Warning Letters to companies illegally selling MK-677/Ibutamoren." FDA.gov, 2023–2024.
[pubmed] Chapman IM, et al. "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects." J Clin Endocrinol Metab, 1996;81:4249-4257.
[clinical-trial] 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;149:601-611.

Related peptides

Ipamorelin

A selective ghrelin receptor agonist that stimulates GH release without the cortisol, prolactin, or ACTH spike seen with older GHRPs like GHRP-6.

CJC-1295

A long-acting GHRH analog engineered with a DAC linker that binds serum albumin, extending half-life from minutes to approximately 8 days.

Sermorelin

The N-terminal 29 amino acids of native GHRH — a former FDA-approved diagnostic and pediatric GH-deficiency therapy, now widely compounded for adult anti-aging protocols.

Macimorelin

An orally active ghrelin receptor agonist FDA-approved in 2017 as a diagnostic test for adult growth hormone deficiency — the only oral alternative to the insulin tolerance test.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.