This study sought to determine whether MK-677, an oral ghrelin mimetic, could prevent the decrease in fat-free mass and decrease intra-abdominal (visceral) fat in healthy older adults with an acceptable tolerability. This 2-year double-blind, randomized, placebo-controlled, modified-crossover study enrolled 65 men and women aged 60 to 81 years. The daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to levels observed in healthy young adults without serious adverse effects. While fat-free mass decreased in the placebo group, it increased in the MK-677-treated individuals (-0.5 kg vs. 1.1 kg, p<0.001). However, no significant differences were observed in intra-abdominal fat or total body fat mass, but there was an increase in limb fat in the MK-677 group compared to the placebo group (1.1 kg vs. 0.24 kg, p=0.001). Finally, body weight increased in both groups but the increase was greater in the MK-677 group (p=0.003). Side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Although MK-677 appeared to restore endogenous growth hormone levels in a physiological secretary pattern, long-term studies in elderly individuals are clearly needed to better document the benefit/risk ratio of this approach.
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