Cardiovascular Events in Adults with Type 2 Diabetes and ASCVD Initiating Once-Weekly Semaglutide vs DPP-4is in the USA

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular benefits in trials involving high-risk patients with type 2 diabetes (T2D), while dipeptidyl peptidase 4 inhibitors (DPP-4is) have not. However, DPP-4is are still commonly prescribed in patients with T2D and atherosclerotic cardiovascular disease (ASCVD). This study compared time to occurrence of cardiovascular events, health care resource utilization (HCRU), and medical costs in patients with T2D and ASCVD who initiated once-weekly semaglutide vs a DPP-4i. Two separate observational cohort analyses were conducted using Optum’s de-identified Clinformatics® Data Mart Database (CDM) and Komodo Healthcare Map™ (January 1, 2018 to September 30, 2022). Patients had T2D and ASCVD and received semaglutide or a DPP-4i. Baseline characteristics were balanced using inverse probability of treatment weighting. After weighting, the CDM analysis included 14,461 semaglutide users and 38,630 DPP-4i users and the Komodo Healthcare Map analysis included 48,303 semaglutide users and 109,179 DPP-4i users. In CDM, semaglutide users had significantly decreased risk of stroke (hazard ratio [HR], 0.54), myocardial infarction (HR 0.64), and their composite (HR 0.59) vs DPP-4is. Semaglutide users also had fewer ASCVD-related and all-cause hospitalizations and outpatient visits and lower ASCVD-related and all-cause hospitalization and total medical costs. Results from Komodo Health were generally consistent with those from CDM. Semaglutide users had significantly reduced risk of cardiovascular outcomes, HCRU, and medical costs compared with DPP-4is. This corroborates results from prior studies of once-weekly GLP-1 RAs and reinforces the important role of semaglutide treatment for patients with T2D and ASCVD. Graphical abstract available for this article. Certain medicines, such as once-weekly semaglutide, have heart benefits in patients with type 2 diabetes (T2D). Other medicines, such as dipeptidyl peptidase 4 inhibitors (DPP-4is), do not. However, patients with T2D and atherosclerotic cardiovascular disease (ASCVD) are still often treated with DPP-4is. This study compared outcomes in patients with T2D and ASCVD taking once-weekly semaglutide or a DPP-4i. Patient data were gathered from two large databases between January 1, 2018 and September 30, 2022. Patient groups were weighted to balance characteristics such as age and weight. Analyses were performed separately in each database. The first database included over 14,000 semaglutide users and over 38,000 DPP-4i users. The second database included over 48,000 semaglutide users and nearly 110,000 DPP-4i users. In the first database, semaglutide users had lower risk of stroke and/or heart attack compared with DPP-4i users. Semaglutide users had fewer hospitalizations and outpatient visits and lower hospitalization and total medical costs. Results from the second database were generally consistent with those from the first. This study showed that semaglutide users had reduced risk of heart-related outcomes compared with DPP-4i users. Semaglutide users used fewer health care resources and had lower medical costs. This supports results from prior studies and demonstrates the importance of semaglutide treatment for patients with T2D and ASCVD.