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

Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE Jr, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO · Annals of Internal Medicine

Twenty-four-hour growth hormone rose 1.8-fold and IGF-1 1.5-fold, reaching the young-adult range in 22 of 43. Fat-free mass rose 1.1 kg (95 percent CI 0.7 to 1.5) against a 0.5 kg fall on placebo (p under 0.001) and body weight rose 2.7 kg against 0.8 kg, with no change in visceral fat and more limb fat on the drug. Strength did not change in knee extension or flexion, and no measure of function or quality of life changed. Fasting glucose rose 0.3 mmol/L and HbA1c 0.2 points with insulin sensitivity reduced, cortisol rose, femoral-neck bone density fell slightly relative to placebo, and LDL cholesterol fell 0.14 mmol/L. Appetite increased in 67 percent against 36 percent; joint pain was reported by 58 percent on the drug and 77 percent on placebo, and two women on the drug withdrew for joint pain after dose reduction.

Population

Healthy men and women aged 60 to 81 at one university centre; 71 randomised, 65 completing the first year

Intervention

MK-677 (ibutamoren) 25 mg orally once daily for one year, with a modified crossover second year

Comparator

Placebo, double-blind

Limitations

Sixty-five healthy older people at one centre, powered for body composition and not, as the authors say, for functional endpoints; the second year is exploratory and six participants were treated for less than two years because the drug expired. Investigator-initiated and funded by the National Institutes of Health, with the drug and placebo supplied by Merck. Joint pain was recorded as an adverse event, not measured as an outcome.