Background Glucagon-like peptide-1 (GLP-1)-based therapies have been shown to improve cardiovascular (CV) risk markers in people with overweight/obesity and established atherosclerotic cardiovascular disease (ASCVD) in clinical trials. However, real-world discontinuation rates exceed those in trials, and patients may not experience the full cardiometabolic benefit. Methods Using Optum EHR-claims linked data, we identified adults with ASCVD prescribed weekly injectable semaglutide or tirzepatide who experienced an improvement in a cardiometabolic parameter on treatment (“responder”) and subsequently discontinued therapy (≥60-day gap in therapy) between 2010-2024. Separate cohorts were constructed based on measures available for the following cardiometabolic markers: weight, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), total cholesterol (TC), and triglycerides (TG). Measures were ascertained at baseline (<90 days before start), discontinuation (±60 days), and within 365+45 days post-discontinuation. Results Overall, 4,860 ASCVD patients were included, of whom 95.6% had a history of type 2 diabetes. Among patients with qualifying cardiometabolic data, 75.2% (N=2,726/3,625) lost weight on therapy. Additionally, patients frequently experienced reductions in other cardiometabolic parameters on therapy, including SBP (57.1%; N=2,062/3,611), HbA1c (81.7%; N=1,973/2,415), TC (71.5%; N=731/1,023), and TG (67.9%; N=693/1,021). Among responders who discontinued GLP-1-based therapy, worsening in cardiometabolic parameters post-discontinuation was frequent, including increases in weight, SBP, HbA1c, TC, and TG in 45.6%, 60.5%, 48.1%, 53.5%, and 37.2% of patients, respectively. Conclusions Among patients with a favorable cardiometabolic response to GLP-1-based therapy who subsequently discontinued treatment, worsening of cardiometabolic parameters was common post-discontinuation, further supporting the need for strategies to improve persistence on therapy in patients with ASCVD. Is this an encore abstract? No
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Edmonston et al. (2026) studied this question.
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