Cardiac safety of chronic inhibition of the myostatin–activin pathway with bimagrumab in healthy older adults

CONTEXT: GLP-1 receptor agonists have revolutionized the treatment of obesity and type 2 diabetes, but may cause excess muscle loss. Inhibitors of the myostatin-activin pathway can cause fat loss and skeletal muscle gain, but the effect of chronic pathway inhibition on human cardiac muscle is not known. OBJECTIVE: Investigate the effects of extended inhibition of the myostatin-activin pathway on cardiovascular parameters in healthy older adults. DESIGN: Randomized, double-blind, placebo-controlled study with 6 months of treatment and up to 6 months of follow-up. SETTING: Single commercial study site. PARTICIPANTS: 68 healthy community-living men and women aged 60 to 86 years. INTERVENTIONS: Intravenous bimagrumab 10 mg/kg or placebo. MAIN OUTCOME MEASURES: Cardiac magnetic resonance assessment of changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Changes in total lean body mass (LBM) and total body fat mass (FM) by dual energy X-ray absorptiometry (DXA). RESULTS: At 6 months, no clinically relevant change was observed in LVMI (least squares mean [90% confidence interval] 1.6 g/m2 [-0.2, 3.4], P = .148) or LVEF (2.0% [-0.4, 4.4], P = .176) between treatments. Total LBM (mean [standard deviation]) increased by 5.5% [3.6], and FM decreased by -14% [8.9] with bimagrumab vs placebo (both P < .001). CONCLUSION: Six months of myostatin-activin pathway inhibition with bimagrumab had no effect on cardiac structure or function in healthy older adults compared to placebo. These results support consideration of bimagrumab as a skeletal muscle-sparing intervention in adults undergoing weight loss with GLP-1 receptor agonists.