Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults - a randomized trial

Two-year randomized, placebo-controlled trial in 65 healthy adults aged 60 to 81 years, conducted at the University of Virginia. The study was designed to answer a direct clinical question: does pharmacological restoration of the GH/IGF-1 axis by an oral secretagogue translate into improvement of body composition, strength and function in healthy elderly?

Participants received 25 mg/day of oral MK-677 or placebo. MK-677 elevated GH and IGF-1 levels to values comparable to those of healthy young adults throughout the study — confirming the robustness and sustainability of the secretagogue effect in aging. The increase was pulsatile and physiologic, without significant desensitization of the somatotropic axis over the 2 years.

In body composition, the result was positive but modest: lean body mass (FFM) increased by 1.1 kg in the MK-677 group, while it decreased by 0.5 kg with placebo (p<0.001 between groups). The gain occurred predominantly in the first 6 weeks and then plateaued. In contrast, there was no improvement in muscle strength or functional performance (gait tests, sit-to-stand) — signaling that the induced hypertrophy did not become functionally useful musculature.

Adverse effects included increase in fasting glycemia by ~0.3 mmol/L and decline in insulin sensitivity, along with appetite increase and transient edema. This study served as an important brake on MK-677 development for sarcopenia: it confirmed that stimulating the GH axis in healthy elderly increases measurable lean mass, but does not deliver the clinically relevant outcome (strength and function). It remains, however, a fundamental reference for the efficacy and safety profile of the compound in prolonged use.