Effectiveness and safety of empagliflozin in routine care patients: results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study

Objective: Over 99% of the EMPA-REG OUTCOME trial participants had established cardiovascular disease (CVD). We aimed to investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin vs dipeptidyl peptidase-4 inhibitor (DPP-4i) across the broad spectrum of cardiovascular risk.Methods: In a population-based cohort study we identified 39,072 pairs of 1:1 propensityscore-matched adult patients with type 2 diabetes (T2D) initiating empagliflozin or dipeptidyl peptidase-4 inhibitor (DPP-4i), using data from 2 U.S. commercial insurance databases and Medicare between 08/2014–09/2017. Primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLA), diabetic ketoacidosis (DKA),and acute kidney injury (AKI). We estimated pooled hazard ratios (HR) and 95% CI adjusting for >140 baseline covariates.Results: Study participants had mean age of 60 years and only 28% had established cardiovascular disease (CVD). Compared to dipeptidyl peptidase-4 inhibitor (DPP-4i), empagliflozin was associated with similar risk of myocardial infarction (MI)/stroke [HR (95% CI), 0.99 (0.81–1.21)], and lower risk of hospitalization for heart failure (HHF) [0.48 (0.35–0.67) and 0.63 (0.54–0.74), based on a primary and any heart failure HF discharge diagnosis, respectively]. The heart failure HF was 0.52 (0.38–0.72) for all-cause mortality (ACM) and 0.83 (0.70–0.98) for a composite of myocardial infarction MI/stroke/ all-cause mortality ACM. Empagliflozin was associated with a similar risk of lower-limb amputations LLA and fractures, an increased risk of diabetic ketoacidosis DKA [1.71 (1.08–2.71)], and a decreased risk of acute kidney injury  AKI [0.60 (0.43–0.85)].Conclusions: In clinical practice, the initiation of empagliflozin vs dipeptidyl peptidase-4 inhibitor DPP-4i was associated with a lower risk of hospitalization for heart failure (HHF), all-cause mortality (ACM), and myocardial infarction (MI)/stroke/ all-cause mortality (ACM),a similar risk of myocardial infarction (MI)/stroke, and a safety profile consistent with documented information.