Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a)

Obesity is associated with blunted GH secretion and an unfavorable lipoprot ein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m(2) and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum Lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not ch anged at study end. Serum total cholesterol and low density Lipoprotein (LD L) cholesterol (LDL-C) levels were not significantly changed by MK-677 trea tment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increas ed at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 week s. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs, placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 w eeks (P = NS vs. placebo). The level of serum triglycerides was increased a t 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activit y in abdominal and gluteal sc adipose tissue was not affected by active tre atment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circ ulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C r atio was decreased, MK-677 treatment did not significantly affect serum Lp( a) concentrations at the present dose and administration protocol.