First Non-Peptide Drug That Mimics Growth Hormone-Releasing Peptide Works in Humans
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.
Quick Facts
What This Study 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.
Key Numbers
How They Did This
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.
Why This Research 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).
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.
What This Study Doesn't 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.
Questions This Raises
- ?Could this approach lead to effective oral growth hormone therapies?
- ?Would the benefits extend to aging or GH-deficient populations?
Trust & Context
- Key Stat:
- 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
- Evidence Grade:
- Strong — randomized controlled trial in human subjects with clear dose-response relationship. Limited by small size and single-dose IV design.
- Study Age:
- Published in 1993 (33 years ago). This research led to MK-677 (ibutamoren) and other oral GH secretagogues now in clinical use or study.
- Original Title:
- Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.
- Published In:
- The Journal of clinical endocrinology and metabolism, 77(5), 1393-7 (1993)
- Authors:
- Gertz, B J(5), Barrett, J S, Eisenhandler, R, Krupa, D A, Wittreich, J M, Seibold, J R, Schneider, S H
- Database ID:
- RPEP-00264
Evidence Hierarchy
Frequently Asked 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 More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00264APA
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.
MLA
Gertz, B J, et al. "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, 1993.
RethinkPeptides
RethinkPeptides Research Database. "Growth hormone response in man to L-692,429, a novel nonpept..." RPEP-00264. Retrieved from https://rethinkpeptides.com/research/gertz-1993-growth-hormone-response-in
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.