Oral semaglutide trial to assess muscle mass safety in Duchenne Muscular Dystrophy with obesity

Duchenne Muscular Dystrophy (DMD) is a severe genetic disease causing progressive muscle weakness, often leading to early death. Approximately half of DMD patients experience overweight or obesity, exacerbated by limited mobility and steroid treatments. While GLP-1 Receptor Agonists (GLP-1 RAs) effectively promote weight loss in the general population and offer cardiovascular benefits, there's a critical concern: their potential to decrease muscle mass, which could be detrimental in DMD. This study addresses the urgent need to evaluate GLP-1 RA safety and tolerability in DMD, specifically regarding muscle health.

This randomized controlled trial (RCT) will enroll adolescents and young adults with Duchenne Muscular Dystrophy (DMD) and obesity. Participants will receive either oral semaglutide or a placebo daily for 24 weeks. Following the RCT, all participants will enter a 40-week open-label extension, receiving oral semaglutide daily. Primary endpoints focus on muscle health, with assessments including body MRI to evaluate muscle and fat tissue, laboratory testing, and mixed meal tolerance tests.

As this is a study protocol, no findings are available yet. The investigators hypothesize that oral semaglutide will be well-tolerated in individuals with DMD and obesity. The primary expectation is that the intervention will decrease fat mass without significantly reducing muscle mass. Secondary hypotheses include positive impacts on weight, glucose and insulin levels, and heart and lung function. The study will also monitor activity levels, mood, gastrointestinal symptoms, and quality of life to provide a comprehensive safety and tolerability profile.

The core hypothesis is that GLP-1 RAs will be well-tolerated and decrease fat mass, critically without a large decrease in muscle mass in this vulnerable population.