Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults A Randomized Trial
Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, 0.5 kg [95% CI, 1.1 to 0.2 kg] vs. 1.1 kg [CI,0.7 to 1.5 kg], respectively; P 0.001), as did body cell mass, as reflected by intracellular water (change, 1.0 kg [CI, 2.1 to 0.2kg] vs. 0.8 kg [CI, 0.1 to 1.6 kg], respectively; P 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs.0.24 kg; P 0.001). Body weight increased 0.8 kg (CI, 0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P 0.015), and insulin sensitivity decreased. The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, 0.14 mmol/L [CI,0.27 to 0.01 mmol/L]; 5.4 mg/dL [CI, 10.4 to 0.4 mg/ dL]; P 0.026); no differences between the groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 g/dL [CI, 1.0 to 2.6 g/dL]) in MK- 677 recipients (P 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.