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First Non-Peptide Drug That Mimics Growth Hormone-Releasing Peptide Works in Humans

RPEP-002641993Gertz, B J; Barrett, J S; Eisenhandler, R; Krupa, D A; Wittreich, J M; Seibold, J R; Schneider, S H
RCTStrong evidence
The takeaway

L-692,429 — a small molecule mimicking GHRP-6 — produced dose-dependent growth hormone release in healthy men at up to 1 mg/kg IV, comparable to GHRH.

24 healthy men, dose-dependent

L-692,429 at 1 mg/kg IV matched the GH-releasing effect of GHRH — first non-peptide to achieve this in humans

What the researchers found

L-692,429 (0.001-1.0 mg/kg IV) produced dose-dependent GH release in healthy young men. At 1 mg/kg, response was comparable to GHRH-(1-29). Safe and well tolerated.

Why it matters

This proved that small molecules can activate the same receptor as growth hormone-releasing peptides. It paved the way for oral GH secretagogues like MK-677 (ibutamoren).

How the study worked

Double-blind, placebo-controlled, incremental dose study in 24 healthy non-obese males aged 18-26. L-692,429 given as 15-min IV infusion. GH measured serially. Safety monitoring included.

What this study cannot tell us

Small phase I study in healthy young men only. Short-term safety only. IV route not practical for clinical use. Did not test repeated dosing or older populations.

How to read the evidence

Strong — randomized controlled trial in human subjects with clear dose-response relationship. Limited by small size and single-dose IV design.

When this study was published

Published in 1993 (33 years ago). This research led to MK-677 (ibutamoren) and other oral GH secretagogues now in clinical use or study.

The bigger picture

This was a pivotal moment in growth hormone research — proving you could take a peptide's effect and recreate it with a small molecule drug. This led directly to the development of oral GH secretagogues, transforming the field from injectable peptides to potential pills.

Questions still open

  • Could this approach lead to effective oral growth hormone therapies?
  • Would the benefits extend to aging or GH-deficient populations?

Common questions

What is a GH secretagogue?
A substance that stimulates the body to release its own growth hormone, rather than injecting synthetic GH. Secretagogues work through the ghrelin receptor to trigger natural pulsatile GH release.
How did this lead to MK-677?
L-692,429 proved the concept but required IV injection. Researchers then developed MK-677 (ibutamoren), which works through the same mechanism but can be taken orally — making it far more practical for clinical use.

Read the original research

Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.

The Journal of clinical endocrinology and metabolism, 77(5), 1393-7

View on PubMed ↗

Citation

Gertz, B J; Barrett, J S; Eisenhandler, R; Krupa, D A; Wittreich, J M; Seibold, J R; Schneider, S H. (1993). Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.. The Journal of clinical endocrinology and metabolism, 77(5), 1393-7.