Effects of Empagliflozin on Cardiovascular Outcomes Are Consistent Across Sociodemographic Subgroups: A Real-World Analysis From the EMPRISE Study

OBJECTIVE: We aimed to explore the heterogeneity of empagliflozin treatment effects on major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and all-cause mortality (ACM) across sociodemographic and cardiovascular disease (CVD) subgroups of adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Using 2014-2020 Medicare claims data, we examined rates of MACE (e.g., composite myocardial infarction, stroke, all-cause mortality [ACM]), HHF, and ACM among propensity score-matched individuals aged ≥65 years with T2D initiating empagliflozin compared with those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) and those prescribed GLP-1 receptor agonists (GLP-1RAs). We calculated hazard ratios (HRs) and incidence rate differences (IRDs) overall and by age, sex, race or ethnicity, socioeconomic factors, and baseline CVD. RESULTS: Empagliflozin was associated with decreased risk of MACE (HR 0.77, 99.9% CI [0.69, 0.85]; IRD = -10.3 [-14.1, -6.4]); HHF (HR 0.72 [0.67, 0.79]; IRD = -18.3 [-22.9, -13.6]); and ACM (HR 0.66 [0.57, 0.76]; IRD = -8.6 [-11.4, -5.8]) compared with DPP4is. Effect heterogeneity by baseline CVD was present across all outcomes on the IRD scale but only for HHF on the HR scale. Empagliflozin was also associated with decreased risk of HHF (HR 0.88 [0.81, 0.95]; IRD = -6.9 [-10.8, -3.1]) versus GLP-1RAs, with effect heterogeneity by baseline CVD on the IRD scale. No effect heterogeneity was observed by sociodemographic factors, although a numeric trend suggested greater absolute benefit in patients aged ≥75 years compared with those aged 65-74 years. CONCLUSIONS: Empagliflozin reduced cardiovascular events across sociodemographic and CVD subgroups compared with both DPP4is and GLP-1RAs, with higher absolute benefits observed in those with prevalent CVD.