Two-month treatment of obese subjects with the oral growth hormone (GH) secretagogue MK-677 increases GH secretion, fat-free mass, and energy expenditure.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled trial
PubMed 9467542 · doi:10.1210/jcem.83.2.4539
What was done
Twenty-four healthy obese men (aged 18–50 years, BMI > 30 kg/m2, waist/hip ratio > 0.95) were randomized in a double-blind, parallel, placebo-controlled trial to receive oral MK-677 25 mg daily (n = 12) or placebo (n = 12) for 8 weeks. Researchers evaluated GH, prolactin, serum IGF-I, IGFBP-3, cortisol, body composition (via DEXA and a four-compartment model), basal metabolic rate, fasting glucose and insulin, and oral glucose tolerance.
What was found
Serum IGF-I increased approximately 40% with MK-677 (P < 0.001 vs. placebo), and IGFBP-3 also increased significantly (P <= 0.001 vs. placebo). GH and prolactin peak and AUC values rose significantly after the first dose and remained elevated at 2 and 8 weeks (except peak prolactin). Serum and urinary cortisol were not elevated at 2 and 8 weeks (P = NS). Fat-free mass increased significantly on DEXA (P < 0.01) and the four-compartment model (P < 0.05), whereas total and visceral fat were unchanged. Basal metabolic rate increased at 2 weeks (P = 0.01) but not at 8 weeks (P = 0.1). Fasting glucose and insulin were unchanged, but oral glucose tolerance was impaired at 2 and 8 weeks.
Why it matters
This study shows that oral MK-677 produces sustained stimulation of the GH/IGF-I axis and increases fat-free mass in obese males. However, it failed to decrease fat mass and worsened glucose tolerance, highlighting key clinical trade-offs.
Limits
The sample size was very small (24 subjects total, 12 per group) and included only adult men. The 8-week duration was too short to determine whether fat loss would eventually occur or to characterize the long-term clinical risks of impaired glucose tolerance.
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