Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Agonist) Therapy.

Background: The long-acting glucagon-like peptide-1 receptor agonist semaglutide is used to treat type 2 diabetes or obesity in adults. Clinical trials have observed associations of semaglutide with weight loss, improved diabetic control, and cardiovascular risk reduction. Objective: To evaluate intrapatient changes in body composition after initiation of semaglutide therapy by applying an automated suite of CT-based artificial intelligence (AI) body composition tools. Methods: This retrospective study included adult patients with semaglutide treatment who underwent abdominopelvic CT both within 5 years before and within 5 years after semaglutide initiation, between January 2016 and November 2023. An automated suite of previously validated CT-based AI body composition tools was applied to pre-semaglutide and post-semaglutide scans to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, skeletal muscle area and attenuation, intermuscular adipose tissue (IMAT) area, liver volume and attenuation, and trabecular bone mineral density (BMD). Patients with ≥5-kg weight loss and ≥5-kg weight gain between scans were compared. Results: The study included 241 patients (mean age, 60.4±12.4 years; 151 women, 90 men). In the weight-loss group (n=67), the post-semaglutide scan, versus pre-semaglutide scan, showed decrease in VAT area (341.1 vs 309.4 cm², p<.001), SAT area (371.4 vs 410.7 cm², p<.001), muscle area (179.2 vs 193.0, p<.001), and liver volume (2379.0 vs 2578 HU, p=.009), and increase in liver attenuation (74.5 vs 67.6 HU, p=.03). In the weight-gain group (n=48), the post-semaglutide scan, versus pre-semaglutide scan, showed increase in VAT area (334.0 vs 312.8, p=.002), SAT area (485.8 vs 488.8 cm², p=.01), and IMAT area (48.4 vs 37.6, p=.009), and decrease in muscle attenuation (5.9 vs 13.1, p<.001). Other comparisons were not significant (p>.05). Conclusion: Patients using semaglutide who lost versus gained weight demonstrated distinct patterns of changes in CT-based body composition measures. Those with weight loss exhibited overall favorable shifts in measures related to cardiometabolic risk. Muscle attenuation decrease in those with weight gain is consistent with decreased muscle quality. Clinical Impact: Automated CT-based AI tools provide biomarkers of body composition changes in patients using semaglutide beyond that which is evident by standard clinical measures.