Association of Cardiovascular Outcomes with Bempedoic Acid vs. Ezetimibe Added to Moderate-Intensity Statin Therapy in People with Type 2 Diabetes

Introduction and Objective: Many people with type 2 diabetes remain at high residual cardiovascular risk despite statin therapy. Ezetimibe is typically the first-line non-statin, although data from CLEAR Outcomes suggest cardiovascular benefit with bempedoic acid, though in a statin-intolerant population. Whether bempedoic acid or ezetimibe offers more favorable real-world cardiovascular outcomes when added to moderate-intensity statin therapy is unknown. Methods: This was a retrospective cohort study using the TriNetX real-world database across 112 healthcare organizations with over 130 million patients. Adults age 18 years or older with type 2 diabetes on moderate intensity statin therapy initiating bempedoic acid or ezetimibe were 1:1 propensity-matched on demographics, cardiovascular risk factors, relevant medications, and laboratory measures. The analysis was performed on Dec 9, 2025, with a one-year look-back for inclusion of baseline characteristics. Outcomes were evaluated in a 10-year follow-up window following an index date where inclusion criteria were met, and included a composite endpoint of first stroke, myocardial infarction, and new onset heart failure. Kaplan-Meier analysis was performed with calculation of risk ratios and 95% confidence intervals for outcomes. Results: After matching 2,990 people were included (N=1,495 in each cohort). Cohorts were well-balanced after matching. Bempedoic acid was associated with a significantly lower risk of the composite cardiovascular endpoint compared with ezetimibe (RR: 0.65, 95% CI: 0.52-0.82, P <0.001). Individual endpoints all favored bempedoic acid. A greater mean change in LDL-C from baseline to end of study was observed with ezetimibe versus bempedoic acid (-30.9 mg/dL vs -21 mg/dL). Conclusion: Among adults with type 2 diabetes on moderate-intensity statin therapy, addition of bempedoic acid was associated with a significantly lower risk of stroke, myocardial infarction, and new onset heart failure versus ezetimibe. Disclosure: B. Ansong: None. R. White: Research Support; Ended; Abbott Diabetes. K. Cowart: Research Support; Ended; Abbott Diabetes, Sanofi.