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. The first cardiovascular outcomes trial (CVOT) to show cardio protection was EMPA-REG OUTCOME, in which empagliflozin rapidly reduced the risk of hospitalisation for heart failure (HHF) and CV death compared with placebo, independently of glycaemic control.
Efforts are now underway to collect real-world evidence (RWE) that may help to bridge this gap, providing insights into how beneficial CV effects seen in CVOTs are reflected in real-world populations and everyday clinical decision-making scenarios.
EMPRISE is an ongoing RWE study of data collected from US healthcare databases, comparing outcomes in patients newly initiated with empagliflozin vs DPP-4 inhibitors. The study will complement the findings of EMPA-REG OUTCOME with routine clinical practice data that encompasses a more diverse patient population, including a broader spectrum of CV risk, and an active comparator that prescribers currently use in a similar position to empagliflozin in the treatment pathway.
The first data from Europe, Israel and East Asia in the EMPRISE RWE study have been presented, revealing a risk reduction in cardiovascular outcomes associated with empagliflozin compared to DPP-4 inhibitors. These results are based on over 130 000 adults with T2D, with or without cardiovascular disease, showing a:
- 45% relative risk reduction (RRR) in all-cause mortality
- 29% RRR in hospitalisation for heart failure
- 33% RRR in a composite endpoint including heart attack, stroke and all-cause mortality.
The EMPRISE findings confirmed empagliflozin’s well-established safety profile. Empagliflozin was not associated with a risk of acute kidney injury – analyses showed a 51% RRR in acute kidney injury requiring dialysis. There was a similar risk of lower limb amputation and bone fractures as with DPP-4 inhibitors. In addition, there was an increased risk of diabetic ketoacidosis, which is consistent with empagliflozin’s known safety information.
The key CV benefits shown in EMPA-REG OUTCOME were reduced risks of CV death and HHF. More broadly, SGLT2 inhibitor CVOTs have consistently shown a reduced risk of HHF vs placebo, whereas a reduction in CV death has thus far been unique to empagliflozin. Consequently, important questions remain about class effect with SGLT2 inhibitors that RWE may help to address.
Findings from the EMPRISE real-world evidence study complement insights from the EMPA-REG OUTCOME trial, which showed that empagliflozin provides cardiovascular and renal benefits, in addition to metabolic effects, in people with T2D and established cardiovascular disease. The EMPA-REG OUTCOME trial found that empagliflozin reduced the relative risk of hospitalisation for heart failure by 35%, all-cause mortality by 32% and incident or worsening kidney disease by 39%, compared to placebo. The role of RWE in complementing CVOTs is increasingly being recognised. The advantages of a cohort of 200 000 patients cannot be denied, and such a large-scale study would not be feasible under RCT conditions. It is hoped that this large cohort will provide additional context to CVOT-generated insights into CV protection.
References available on request.