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

Year: 2026

Type: preprint

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. Article Highlights Why did we undertake this study? Rapid uptake of GLP-1 RAs has outpaced evidence on long-term muscle change during routine treatment. What is the specific question we wanted to answer? We asked whether GLP-1 RA initiation was associated with excess muscle and fat loss versus matched controls with diabetes. What did we find? Over 4.6 years, initiators lost roughly 60% more skeletal muscle than matched controls (−2.75 percentage points) alongside greater weight loss. Each additional kilogram lost was accompanied by about 100 mL of additional muscle loss. What are the implications of our findings? Skeletal muscle loss is a measurable component of GLP-1 RA-associated weight loss in routine care. Muscle mass should be monitored during treatment, and muscle-preservation strategies such as resistance training and adequate protein intake need evaluation.

Source: medRxiv

DOI: 10.64898/2026.09.15.26363157