Author(s): JOHNSSON, K., DE FILIPPIS, E., BURAS, M., KATSANOS, C., Institution: ARIZONA STATE UNIVERSITY, Country: UNITED STATES, Abstract-ID: 2582

INTRODUCTION:
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for weight loss. However, concomitant loss of muscle mass is a documented concern. The extent of muscle loss outside of controlled clinical trials remains poorly characterized¹.
METHODS:
We examined 3-month changes in muscle mass and evaluated baseline predictors of this change in 51 (39 female) patients receiving GLP-1 treatment at Mayo Clinic. Body composition was assessed via bioelectrical impedance analysis (BIA; Tanita Corporation, Inc.) at baseline and after 3 months of GLP-1RA treatment. Baseline characteristics were: age, 49±12 (mean±SD) years; body weight 112 ± 27 kg; body mass index (BMI), 39±8 kg/m²; muscle mass, 58±12 kg; and body fat, 44±7 %. Backward stepwise multiple linear regression was used to evaluate predictors of muscle mass changes, including age, sex, medication type and achieved dose, and baseline anthropometrics (body weight, BMI, muscle mass, and fat mass). Model assumptions were assessed using residual plots, multicollinearity was evaluated with variance inflation factors, and model fit was summarized using R². A minimal clinically important decrease in muscle mass at 3 months was estimated as 0.1 multiplied by the baseline between-subject SD².
RESULTS:
Mean muscle mass decreased significantly at 3 months (58±12 vs. 56±12 kg; P = 0.0163). Regression analysis revealed that higher baseline muscle mass (P = 0.0013) and female sex (P = 0.0087) were associated with greater muscle loss, whereas higher baseline body weight was associated with muscle preservation (P = 0.0021). Age, medication type, and achieved dose were not significant predictors of muscle changes (P > 0.05). The final model explained approximately 37% of the variance (R² = 0.37), indicating that 63% of inter-individual variability was not accounted for by baseline anthropometrics. Based on our clinically conservative threshold of important decrease in muscle mass, 27 participants experienced significant muscle loss. Notably, 13 participants demonstrated an increase in muscle mass over the same period, illustrating divergent responses of muscle mass changes during GLP-1RA treatment.
CONCLUSION:
In a real-world setting, GLP-1RA therapy is associated with an overall decline in muscle mass, yet individual responses may vary considerably. These findings suggest that key determinants beyond baseline anthropometrics, particularly physical activity/exercise and nutrition, established factors regulating muscle mass, should be studied over the course of GLP-1RA treatment to better explain potential changes in muscle mass.

¹ Karakasis, P., et al.(2025). Metabolism: clinical and experimental, 164, 156113. https://doi.org/10.1016/j.metabol.2024.156113
² Mirzadeh, P., et al. (2026). Nutrition, Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2026.104615