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BACKGROUND: Empagliflozin and dapagliflozin have proven cardiovascular benefits in people with type 2 diabetes at high cardiovascular risk, but their comparative effectiveness is unknown. METHODS: This study used nationwide, population-based Danish health registries to emulate a hypothetical target trial comparing empagliflozin versus dapagliflozin initiation, in addition to standard care, among people with treated type 2 diabetes from 2014 through 2020. The outcome was a composite of myocardial infarction, ischemic stroke, heart failure (HF), or cardiovascular death (major adverse cardiovascular event). Participants were followed until an outcome, emigration, or death occurred; 6 years after initiation; or December 31, 2021, whichever occurred first. Logistic regression was used to compute inverse probability of treatment and censoring weights, controlling for 57 potential confounders. In intention-to-treat analyses, 6-year adjusted risks, risk differences, and risk ratios, considering noncardiovascular death competing events, were estimated. Analyses were stratified by coexisting atherosclerotic cardiovascular disease and HF. A per-protocol design was performed as a secondary analysis. RESULTS: There were 36 670 eligible empagliflozin and 20 606 eligible dapagliflozin initiators. In the intention-to-treat analysis, the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% 95% CI, -0.9% to 1.0%; risk ratio, 1.00 95% CI, 0.91 to 1.11). The findings were consistent in people with atherosclerotic cardiovascular disease (risk difference, -2.3% 95% CI, -8.2% to 3.5%; risk ratio, 0.92 95% CI, 0.74 to 1.14) and without atherosclerotic cardiovascular disease (risk difference, 0.3% 95% CI, -0.6% to 1.2%; risk ratio, 1.04 95% CI, 0.93 to 1.16) and in people with HF (risk difference, 1.1% 95% CI, -6.5% to 8.6%; risk ratio, 1.04 95% CI, 0.79 to 1.37) and without HF (risk difference, -0.1% 95% CI, -1.0% to 0.8%; risk ratio, 0.99 95% CI, 0.90 to 1.09). The 6-year risks of major adverse cardiovascular event were also not different in the per-protocol analysis (9.1% versus 8.8%; risk difference, 0.2% 95% CI, -2.1% to 2.5%; risk ratio, 1.03 95% CI, 0.80 to 1.32). CONCLUSIONS: Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes with or without coexisting atherosclerotic cardiovascular disease or HF.
Bonnesen et al. (Thu,) studied this question.