Once-Weekly Semaglutide in Patients with Cardiovascular-Kidney-Metabolic Syndrome: A Real-World Study

Introduction and Objectives: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in the interplay between cardiovascular disease, chronic kidney disease, and metabolic dysfunction. This work analyzed the efficacy and safety of once-weekly semaglutide in patients with cardiovascular-kidney-metabolic syndrome. Patients and Methods: This observational, real-world study included patients with heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus treated with once-weekly semaglutide (Sema-CKM Group) and patients not treated with glucagon-like peptide-1 receptor agonists (Control-CKM Group). A 1:1 propensity score matching analysis was performed. The two primary outcomes were heart failure events and major kidney disease events at 24 months. Results: After matching, 302 patients were included in each group. A heart failure event occurred in 63 patients (20.9%) in the Sema-CKM Group and 121 (40.1%) in the Control-CKM Group (OR: 0.80; 95%CI: 0.62-0.98; p < 0.01). The number of major kidney disease events was lower in the Sema-CKM Group than the Control-CKM Group (36 vs. 65; OR: 0.85; 95%CI: 0.72-0.98; p = 0.014). Patients in the Sema-CKM Group were more likely to have an improvement in heart failure health status from baseline to 24 months (OR: 2.80; 95%CI: 1.30-4.30; p < 0.01). Semaglutide also improved glycemic control (glycated hemoglobin -0.7%) and reduced body weight (-9.3 kg). Conclusions: Once-weekly semaglutide was associated with reductions in heart failure events and major kidney disease events in patients with heart failure, chronic kidney disease, obesity, and type 2 diabetes mellitus. Further research on glucagon-like peptide-1 receptor agonists in cardiovascular-kidney-metabolic syndrome is needed.