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21.03.2024 | Article

Effectiveness and safety of empagliflozin: final results from the EMPRISE study

verfasst von: Phyo T. Htoo, Helen Tesfaye, Sebastian Schneeweiss, Deborah J. Wexler, Brendan M. Everett, Robert J. Glynn, Niklas Schmedt, Lisette Koeneman, Anouk Déruaz-Luyet, Julie M. Paik, Elisabetta Patorno

Erschienen in: Diabetologia

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Abstract

Aims/hypothesis

Limited evidence exists on the comparative safety and effectiveness of empagliflozin against alternative glucose-lowering medications in individuals with type 2 diabetes with the broad spectrum of cardiovascular risk. The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) cohort study was designed to monitor the safety and effectiveness of empagliflozin periodically for a period of 5 years with data collection from electronic healthcare databases.

Methods

We identified individuals ≥18 years old with type 2 diabetes who initiated empagliflozin or dipeptidyl peptidase-4 inhibitors (DPP-4i) from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we identified four a priori-defined effectiveness outcomes: (1) myocardial infarction (MI) or stroke; (2) hospitalisation for heart failure (HHF); (3) major adverse cardiovascular events (MACE); and (4) cardiovascular mortality or HHF. Safety outcomes included lower-limb amputations, non-vertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), severe hypoglycaemia, retinopathy progression, and short-term kidney and bladder cancers. We estimated HRs and rate differences (RDs) per 1000 person-years, overall and stratified by age, sex, baseline atherosclerotic cardiovascular disease (ASCVD) and heart failure.

Results

We identified 115,116 matched pairs. Compared with DPP-4i, empagliflozin was associated with lower risks of MI/stroke (HR 0.88 [95% CI 0.81, 0.96]; RD −2.08 [95% CI (−3.26, −0.90]), HHF (HR 0.50 [0.44, 0.56]; RD −5.35 [−6.22, −4.49]), MACE (HR 0.73 [0.62, 0.86]; RD −6.37 [−8.98, −3.77]) and cardiovascular mortality/HHF (HR 0.57 [0.47, 0.69]; RD −10.36 [−12.63, −8.12]). Absolute benefits were larger in older individuals and in those with ASCVD/heart failure. Empagliflozin was associated with an increased risk of DKA (HR 1.78 [1.44, 2.19]; RD 1.59 [1.08, 2.09]); decreased risks of AKI (HR 0.62 [0.54, 0.72]; RD −2.39 [−3.08, −1.71]), hypoglycaemia (HR 0.75 [0.67, 0.84]; RD −2.46 [−3.32, −1.60]) and retinopathy progression (HR 0.78 [0.63, 0.96)]; RD −9.49 [−16.97, −2.10]); and similar risks of other safety events.

Conclusions/interpretation

Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular mortality or HHF. Absolute risk reductions were larger in older individuals and in those who had history of ASCVD or heart failure. Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression to proliferative retinopathy, with no difference in the short-term risks of lower-extremity amputation, non-vertebral fractures, kidney and renal pelvis cancer, and bladder cancer.

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Titel: Effectiveness and safety of empagliflozin: final results from the EMPRISE study
verfasst von: Phyo T. Htoo
Helen Tesfaye
Sebastian Schneeweiss
Deborah J. Wexler
Brendan M. Everett
Robert J. Glynn
Niklas Schmedt
Lisette Koeneman
Anouk Déruaz-Luyet
Julie M. Paik
Elisabetta Patorno
Publikationsdatum: 21.03.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-024-06126-3

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Effectiveness and safety of empagliflozin: final results from the EMPRISE study

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