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.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 8954023 · doi:10.1210/jcem.81.12.8954023
What was done
Thirty-two healthy elderly subjects (15 women and 17 men, aged 64–81 years) were enrolled in a randomized, double-blind, placebo-controlled trial. Participants received once-daily oral doses of placebo or MK-677 (2, 10, or 25 mg) for two separate study periods of 14 and 28 days. Blood was sampled every 20 minutes over 24 hours at baseline and on day 14 of each period to evaluate pulsatile GH, PRL, and cortisol. IGF-I, IGFBP-3, and fasting glucose were also measured.
What was found
MK-677 produced dose-dependent increases in GH. The 25 mg/day dose increased mean 24-h GH concentration by 97 ± 23% (P < 0.05 vs. baseline) through increases in GH pulse height and interpulse nadir concentrations without changing pulse frequency. Serum IGF-I rose from 141 ± 21 µg/L at baseline to 219 ± 21 µg/L at 2 weeks and 265 ± 29 µg/L at 4 weeks (P < 0.05), reaching young adult reference levels. Fasting glucose increased significantly from 5.4 ± 0.3 mmol/L at baseline to 6.8 ± 0.4 mmol/L at 4 weeks (P < 0.01). PRL increased by 23% (staying within normal range), while cortisol levels showed no significant change.
Why it matters
This trial demonstrates that an oral ghrelin-mimetic/GH secretagogue can restore GH and IGF-I concentrations in older adults to young adult physiological levels by amplifying endogenous pulsatile secretion, though glycemic changes require careful evaluation.
Limits
The study sample was small (n = 32 across four dosage arms) and the intervention duration was short (up to 4 weeks). It only enrolled healthy elderly participants and measured short-term surrogate biochemical markers, without assessing clinical outcomes, body composition, functional status, or long-term safety.
Cited by
- supports Most growth hormone secretagogues carry a risk of insulin resistance and diabetes, particularly at higher doses.