Abstract Body (Do not enter title and authors here): Introduction
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce weight. However, the degree to which this involves loss of fat and/or lean muscle mass remains uncertain, as does the potential for exercise to mitigate these effects.
Aims
To evaluate changes in body composition among patients on GLP-1RAs who completed a structured exercise program of cardiac rehabilitation (CR), compared to patients on GLP-1RAs alone.
Hypothesis
We hypothesized that completion of CR while on a GLP-1RA would be associated with preservation of muscle mass and greater reductions in body fat than GLP-1RA therapy alone.
Methods
We performed a retrospective review of patients who completed CR at our institution between June 2018 and April 2025, identifying 51 patients on a GLP-1RA that underwent bioelectrical impedance analysis (BIA) of body composition before and after CR (GLP-1RA+CR group). A comparison group consisted of patients on GLP-1RAs who did not participate in CR and who underwent BIA during routine follow-up (GLP-1RA group). Demographic and clinical data were obtained from the electronic medical record. Descriptive statistics included chi-square analysis for categorical variables and non-parametric Kruskal-Wallis tests and proportion t-tests for quantitative variables (RStudio, v 2024.12.1+563).
Results
The GLP-1RA+CR and GLP-1RA groups were similar in age (mean 65 vs 61 years; p=0.246) and racial composition, though the GLP-1RA+CR group had more men (76% vs 39%; p<0.001). Median time between BIA analyses was 3 months for the GLP-1RA+CR group and 4 months for the GLP-1RA group. Both groups had similar rates of diabetes (80% vs 83%). Baseline BMI was comparable (mean 30.9 kg/m2 in GLP-1RA+CR group vs 31.2 kg/m2 in GLP-1RA group), with both groups’ BMI dropping 0.5 kg/m2. However, the GLP-1RA+CR group experienced greater percent body fat loss (mean -1.3% vs -0.3%; p=0.026). Notably, skeletal muscle mass increased in the GLP-1RA+CR group (+0.4lbs) but decreased in the GLP-1RA group (-0.7lbs; p=0.041), with greater appendicular muscle mass loss (-2.9lbs vs +0.2lbs; p=0.045). Sex differences were noted such that in women, the GLP-1RA+CR group had even greater body fat loss (-2.1% vs -0.4%; p=0.015) and skeletal muscle gain (1.2lbs vs -0.6lbs; p=0.014).
Conclusions
Our findings suggest exercise may prevent GLP-1RAs from causing skeletal muscle mass loss, while also decreasing markers of adiposity, such as BMI and percent body fat, particularly in women.