Discrepancy between serum leptin values and total body fat in response to the oral growth hormone secretagogue MK-677

Clin Endocrinol (Oxf). 1999 Apr;50(4):451-6. doi: 10.1046/j.1365-2265.1999.00667.x.


Objective: Growth hormone (GH) treatment decreases total body fat while this effect has not yet been documented for the oral GH secretagogue MK-677. In the present study, the effects of MK-677 treatment on serum levels of leptin, thyroid hormones and testosterone were determined.

Design: This was a randomized, double-blind, and parallel study. Twenty-four healthy obese males, 19-49 years of age, with body mass index (BMI) > 30 kg/m2 and a waist:hip ratio > 0.95, were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks.

Results: MK-677 treatment increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment (P < 0.05 vs. placebo) but no significant change was observed at 8 weeks. An increase in serum free 3, 5, 3'-triiodothyronine (free T3) was not detected until 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Peak serum thyroid stimulating hormone (TSH) concentration after MK-677 administration was similar to that after placebo administration at initiation of treatment and at 2 weeks. At 8 weeks of MK-677 treatment, mean peak serum TSH concentration was increased (P < 0.05 vs. placebo) although it remained within the normal range. Serum peak values of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were similar after MK-677 and placebo administration. MK-677 treatment reduced serum total testosterone (P < 0.05 vs. placebo) although total testosterone/sex hormone-binding globulin (SHBG) ratio (an index of free testosterone) was not changed.

Conclusion: Treatment with the oral GH secretagogue MK-677 transiently increased serum leptin levels and leptin/body fat ratio at 2 weeks of treatment, and increased serum free T3 after 8 weeks. These results indicate that MK-677 treatment is able to affect circulating factors of importance for adipose tissue mass and fuel metabolism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Body Composition / drug effects
  • Cholagogues and Choleretics / therapeutic use*
  • Double-Blind Method
  • Drug Administration Schedule
  • Growth Hormone / metabolism*
  • Humans
  • Indoles / therapeutic use*
  • Leptin
  • Linear Models
  • Male
  • Middle Aged
  • Obesity / blood*
  • Obesity / drug therapy
  • Obesity / physiopathology
  • Proteins / metabolism*
  • Spiro Compounds / therapeutic use*
  • Testosterone / blood
  • Thyrotropin / blood
  • Triiodothyronine / blood


  • Cholagogues and Choleretics
  • Indoles
  • Leptin
  • Proteins
  • Spiro Compounds
  • Triiodothyronine
  • Testosterone
  • Thyrotropin
  • Growth Hormone
  • ibutamoren mesylate