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
Authors: Vistisen Dorte , Carstensen Bendix , Elisabetta Patorno , Lanzinger Stefanie , Tan Elise Chia-Hui , Yabe Daisuke , Kim Dae Jung , Sheu Wayne H.-H. , Melzer-Cohen Cheli , Holl Reinhard W. , Núñez Júlio , Ha Kyoung Hwa , Halvorsen Sigrun , Langslet Gisle , Karasik Avraham , Nyström Thomas , Niskanen Leo , Guleria Sonia , Klement Riho , Carrasco Marc , Foersch Johannes , Shay Christina , Koeneman Lisette , Hoti Fabian , Farsani Soulmaz Fazeli , Khunti Kamlesh , Zaccardi Francesco , Subramanian Anuradhaa , Nirantharakumar Krishnarajah ,   EMPRISE EU, Brodovicz Kimberly , Zint Kristina , Försch Johannes , Rosenzweig Doron , Lajer Maria , Overgaard Mikkel , Grip Emilie Toresson , Söreskog Emma , Gunnarsson Joel , Karlsdotter Kristina , Stenman Lotta , Tuovinen Mikko , Valveny Neus , Casajust Paula , Farmer Ruth , Ternouth Andrew , Ofstad Anne Pernille ,   East Asia Study Group, Nangaku Masaomi , Node Koichi , Taneda Yusuke , Yasui Atsutaka , Seino Yutaka , Yi Jingbo , Lei Weiyu , Lee Sunwoo , Lee Jinhee 
Published: September 2023

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.