223-OR: Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)

Introduction and Objective: SURPASS-CVOT is an ongoing, randomized, active-controlled trial evaluating the effect of tirzepatide vs. dulaglutide on major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We aimed to emulate the SURPASS-CVOT trial using insurance claims data. Methods: Using claims from a private health plan (06/2022 to 08/2024), we identified 15,775 pairs of 1:1 propensity score (PS)-matched adults initiating tirzepatide or dulaglutide, stratified by baseline SGLT2i use. Our primary outcome was MACE (myocardial infarction, stroke, or mortality). We estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusting for 125 covariates. We also conducted HbA1c-adjusted analyses among those with HbA1c values (54% of population). Results: Over a median follow up of ~6 months, tirzepatide was associated with a 37% reduction in MACE vs. dulaglutide (Table). Results were consistent in the HbA1c-adjusted analysis (HR, 0.77; 95% CI, 0.62 to 0.95) and, in both analyses, irrespective of SGLT2i use. Conclusion: In this observational study emulating SURPASS-CVOT, tirzepatide appeared superior to dulaglutide in preventing MACE events. This study may also inform the design and conduct of future observational studies evaluating GLP-1-based treatments. Disclosure J. Ostrominski: None. J. Ortega-Montiel: None. H. Tesfaye: None. C. Alix: None. D.J. Wexler: Other Relationship; Novo Nordisk. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.