Evidence from routine clinical practice: EMPRISE provides a new perspective on CVOTs

Abstract

EMPA-REG OUTCOME is recognised by international guidelines as a landmark study that showed a significant cardioprotective benefit with empagliflozin in patients with type 2 diabetes (T2D) and cardiovascular disease. To assess the impact of empagliflozin in routine clinical practice, the ongoing EMPRISE study is collecting real-world evidence to compare effectiveness, safety and health economic outcomes between empagliflozin and DPP-4 inhibitors. A planned interim analysis of EMPRISE was recently published, confirming a substantial reduction in hospitalisation for heart failure with empagliflozin across a diverse patient population. In this commentary article, we discuss the new data in the context of current evidence and clinical guidelines, as clinicians experienced in managing cardiovascular risk in patients with T2D. We also look forward to what future insights EMPRISE may offer, as evidence is accumulated over the next years to complement the important findings of EMPA-REG OUTCOME.

Current trends in diabetes mellitus database research in Japan

“…101,102 To date, most of the studies assessing CV risk reduction associated with SGLT2i compared to that associated with other glucose-lowering drugs (oGLDs), including DPP-4i, have included patients from western countries. [103][104][105][106] The CVD-REAL 2 was the first study that included real-world Japanese patients, which showed a significant CV risk reduction associated with SGLT2i compared to that associated with oGLDs. 107 The results were consistent regardless of CVD history across the countries involved in the study.…”

“…SGLT2i was first introduced in 2014 in Japan, and extensive real‐world data have shown the characteristics of patients receiving SGLT2i treatment as those who tend to be younger, have higher BMIs, and have higher HbA1c levels compared to those in patients receiving non‐SGLT2i treatments 101,102 . To date, most of the studies assessing CV risk reduction associated with SGLT2i compared to that associated with other glucose‐lowering drugs (oGLDs), including DPP‐4i, have included patients from western countries 103–106 . The CVD‐REAL 2 was the first study that included real‐world Japanese patients, which showed a significant CV risk reduction associated with SGLT2i compared to that associated with oGLDs 107 .…”

Reappraisal on pharmacological and mechanical treatments of heart failure

“…The promising results of SGLT-2is may be related to the upregulation of the renin-angiotensinaldosterone system [111]. EMPA-REG OUTCOME [112] is recognized by international guidelines as a landmark study [113]. In the empagliflozin group, there were significantly lower rates of HHF [114], which were achieved by improving diastolic stiffness and hence diastolic function [115] as well as attenuating cardiac fibrosis and improving ventricular haemodynamics [116].…”

How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

“…This suggests that SGLT2 inhibitors have plausible class effects on cardiorenal outcomes [ 5 , 6 ]. Indeed, some large-scale observational cohort studies also demonstrated that initiation of SGLT2 inhibitors compared with other glucose-lowering drugs, such as dipeptidyl peptidase-4 inhibitors, was associated with a decreased risk of cardiorenal events among patients with T2D in clinical practice [ 7 – 10 ].…”