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 propensity score-matched adult patients with T2D initiating empagliflozin or 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 CVD. Compared to DPP-4i, empagliflozin was associated with similar risk of MI/stroke [HR (95% CI), 0.99 (0.81-1.21)], and lower risk of HHF [0.48 (0.35-0.67) and 0.63 (0.54-0.74), based on a primary and any HF discharge diagnosis, respectively]. The HR was 0.52 (0.38-0.72) for all-cause mortality (ACM) and 0.83 (0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA [1.71 (1.08-2.71)], and a decreased risk of AKI [0.60 (0.43-0.85)]. Conclusions In clinical practice, the initiation of empagliflozin vs DPP-4i was associated with a lower risk of HHF, ACM, and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information. This article is protected by copyright. All rights reserved.