Use of Semaglutide and Tirzepatide in Rheumatic and Musculoskeletal Diseases: Insights on Initiation Patterns and Weight Loss From the Rheumatology Informatics System for Effectiveness Registry

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide (SEM) and tirzepatide (TZP) were initially approved for type 2 diabetes management but are increasingly used for weight loss. Limited data exist on real-world use among patients with rheumatic and musculoskeletal diseases (RMDs). This study aimed to describe characteristics and trends in SEM and TZP initiation among individuals with RMDs and to identify factors associated with weight loss. METHODS: We conducted a retrospective analysis using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry. Adults with RMD prescribed SEM or TZP between 2018 and 2024 were included. Patients with an evaluation and management visit before first GLP-1 RA prescription were classified as new users. The primary outcome was percent change in body weight from baseline to 12 months. Multivariable linear regression assessed factors associated with percent weight change, and logistic models identified predictors of ≥5%, ≥10%, and ≥15% weight loss. RESULTS: Among 60,198 patients with RMD treated with GLP-1 RAs (72% SEM), 80.5% were female, and 54.9% had diabetes; the mean age was 57.0 years, and body mass index was 36.4. GLP-1 RA use increased from 0.1% in 2018 to 6.8% in 2024. At 12 months, SEM and TZP users lost 5.8% and 8.2% of body weight, respectively. TZP users lost 2.2% (95% confidence interval [CI] 1.9-2.5) more weight than SEM users, and those without diabetes lost 1.8% (95% CI 1.5-2.1) more than those with diabetes. CONCLUSION: GLP-1 RA use is increasing among patients with RMD and is associated with clinically meaningful weight loss, particularly with TZP and in individuals without diabetes.