GLP-1 Receptor Agonist Initiation Is Associated With Excess Skeletal Muscle Loss in Adults With Diabetes: A Prospective Population-Based MRI Study

Abstract Objective. To determine whether glucagon-like peptide 1 receptor agonist (GLP-1 RA) initiation is associated with excess skeletal muscle loss on repeat whole-body MRI. Research Design and Methods. In the German National Cohort, 58 adults with diabetes who initiated a GLP-1 RA between whole-body MRI examinations 4.6 years apart were matched on sex, age, BMI, and interval to 130 never-exposed controls with diabetes. Deep-learning-segmented tissue volumes were compared within matched sets. Results. Skeletal muscle volume declined 2.75 percentage points more in initiators (95% CI -4.51 to -0.99; P = 0.003), with 2.54 percentage points greater weight loss (P = 0.021). Adipose tissue differences (-4.8% internal torso, -3.2% subcutaneous) were nonsignificant. Conclusions. In this first population-based comparison of whole-body MRI before and after GLP-1 RA initiation with matched unexposed controls, initiators lost roughly 60% more muscle. Skeletal muscle loss is a measurable component of GLP-1 RA weight loss in routine care.