Body composition changes in patients on GLP-1 receptor agonists undergoing an intensive cardiac rehabilitation program

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity and produce significant weight loss. However, concerns have emerged about potential loss of skeletal muscle mass (SMM) with pharmacologic weight reduction, particularly in older adults at risk for sarcopenia. The effects of GLP-1 RA therapy on SMM among patients participating in Intensive Cardiac Rehabilitation (ICR) remain incompletely characterized. METHODS: We performed a retrospective cohort study of 468 patients enrolled in a structured Pritikin ICR program at UC San Diego Health between 2017 and 2024. At program initiation, 67 patients were taking GLP-1 RAs with a median duration of 231 days (IQR 144-400). Body composition was assessed using bioelectrical impedance analysis (BIA) at baseline and program completion. Outcomes included SMM and fat mass (FM). Multivariable regression models adjusted for age, sex, baseline body mass index, diabetes status, and baseline fitness (measured in METs). RESULTS: Both groups improved in metabolic equivalents of task (METs) with ICR (p < 0.001). At baseline, patients on GLP-1 RAs had higher BMI and percent body fat compared with non-users, but no differences in SMM. In adjusted analyses, GLP-1 RA use was not associated with significantly different percent change in SMM from baseline to ICR program completion compared with no GLP-1 RA use (β = 0.62%, 95% CI -0.62 to 1.86; p = 0.326). Similarly, there was no significant between-group difference in percent change in fat mass (β = 3.01%, 95% CI -1.64 to 7.66; p = 0.204). CONCLUSIONS: GLP-1 receptor agonist use during intensive cardiac rehabilitation was not associated with significantly different skeletal muscles mass changes after adjustment for measured covariates. These findings support the integration of GLP-1 based pharmacotherapy with structured exercise programs.