Oral Nutritional Supplements and Body Composition Outcomes Among GLP-1 Receptor Agonist Users: Real-World Evidence

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for obesity and type 2 diabetes treatment, promoting glycemic management and substantial weight loss. However, rapid weight reduction may lead to loss of lean body mass (LBM), especially among malnourished or high-risk patients. Oral nutritional supplements (ONS), which provide protein and micronutrient support, may help preserve LBM and optimize weight-related outcomes during GLP-1RA therapy, but real-world evidence remains limited. Research Design and Methods: We conducted a retrospective cohort study of 252 adult patients treated with GLP-1RAs for obesity and/or type 2 diabetes at an outpatient clinic from January 2018 to January 2025 who had complete data on body composition. Patients diagnosed with protein malnutrition were prescribed ONS. Coarsened Exact Matching (CEM) was used to balance age, sex, diabetes status and GLP-1RA exposure duration between ONS (n=88) and non-ONS (n=32) patients. Weight-related outcomes—body fat ratio, BMI, body fat, LBM, total body weight, and fat-to-LBM loss ratio—were assessed using difference-in-differences regression models. Subgroup analyses were conducted by age, sex, diabetes status, ONS compliance, and duration of GLP-1RA use. Results: ONS use was associated with significantly greater reductions in BMI (− 1.4 kg/m 2 ), body fat (− 8.4 lbs), total weight (− 10.1 lbs), and a 2-percentage-point decrease in body fat ratio (all p< 0.05). While ONS users also lost 5.5 lbs of LBM (p< 0.01), the fat-to-LBM loss ratio remained favorable (2.3, p< 0.01). Subgroup analyses showed the strongest effects among patients younger than 50 years, ONS compliers, those treated with GLP-1RA for 181– 365 days, and patients without diabetes (all p< 0.05). Conclusion: ONS use during GLP-1RA therapy was associated with improved weight loss outcomes and favorable shifts in body composition, particularly among subgroups at higher risk of muscle loss or prolonged treatment. Incorporating ONS into GLP-1RA–based weight management may enhance clinical outcomes while mitigating risks of muscle loss. Keywords: GLP-1 receptor agonists, oral nutritional supplements, lean body mass, body composition, obesity, diabetes