Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia

Dorte Vistisen, Bendix Carstensen, Patorno Elisabetta, Stefanie Lanzinger, Elise Chia Hui Tan, Daisuke Yabe, Dae Jung Kim, Wayne H.H. Sheu, Cheli Melzer-Cohen, Reinhard W. Holl, Júlio Núñez, Kyoung Hwa Ha, Sigrun Halvorsen, Gisle Langslet, Avraham Karasik, Thomas Nyström, Leo Niskanen, Sonia Guleria, Riho Klement, Marc CarrascoJohannes Foersch, Christina Shay*, Lisette Koeneman, Fabian Hoti, Soulmaz Fazeli Farsani, Kamlesh Khunti, Francesco Zaccardi, Anuradhaa Subramanian, Krishnarajah Nirantharakumar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). Methods and results: Adults initiating empagliflozin and DPP-4i in 2014–2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64–0.86), CVM (HR 0.55; 95% CI 0.38–0.80), HHF or CVM (HR 0.57; 95% CI 0.48–0.67) and stroke (HR 0.79; 95% CI 0.67–0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. Conclusion: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

Original languageEnglish
Article number233
JournalCardiovascular Diabetology
Volume22
Issue number1
DOIs
StatePublished - Dec 2023
Externally publishedYes

Funding

FundersFunder number
Boehringer Ingelheim & Lilly Diabetes Alliance
Doron Rosenzweig
Emilie Toresson Grip and Joel Gunnarsson
Johannes Försch
Kansai Electric Power Hospital
Maria Lajer
Syneos Health Clinical K.K.
Yutaka Seino
Boehringer Ingelheim Japan
National Institute for Health and Care Research
University of Birmingham
University of Tokyo
Saga University
NIHR Imperial Biomedical Research Centre
NIHR Leicester Biomedical Research Centre

    Keywords

    • Cardiovascular disease
    • Comparative effectiveness
    • Dipeptidyl peptidase-4 inhibitors
    • Empagliflozin
    • Heart failure
    • Type 2 diabetes

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