Cardiovascular and renal effectiveness of empagliflozin in routine care in East Asia: Results from the EMPRISE East Asia study

Abstract

Aim To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study. Materials and methods Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end‐stage renal disease (ESRD) and all‐cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random‐effects meta‐analysis. Results Overall, 28 712 pairs of PS‐matched patients were identified with mean follow‐up of 5.7‐6.8 months. Compared with DPP‐4 inhibitors, the risk of HHF was reduced by 18% and all‐cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71‐0.94, and HR 0.64; 95% CI 0.50‐0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP‐4 inhibitors (HR 0.37; 95% CI 0.24‐0.58). Conclusions Empagliflozin treatment was associated with reduced risk for HHF, all‐cause mortality and ESRD compared with DPP‐4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan.

Cardiovascular Benefits With Favorable Renal, Amputation and Hypoglycemic Outcomes of SGLT-2 Inhibitors in Type 2 Diabetes From the Asian Perspective: A Population-Based Cohort Study and Systematic Review

“…Lower risks associated with the use of SGLT2is on the safety outcomes of amputation and hospitalized hypoglycemia, which were not assessed in the previous studies of Asian populations, were also observed. These favorable outcomes with SGLT2i use were consistently observed in subgroups stratified by various patient characteristics, which ensures the robustness of our findings as supportive evidence to the existing literature ( 11 , 14 – 22 , 30 ) shown in the systematic review to promote the rational use of SGLT2is in a diverse group of real-world Asian patients with T2D.…”

“…Significant beneficial results were consistently observed across studies, with 14–42% ( 19 , 21 ) and 15–66% ( 11 , 17 ) of risk reductions for HHF and all-cause death associated with the use of SGLT2is versus DPP4is, respectively. A 31–77% reduced risk of ESRD or CKD for the use of SGLT2is versus DPP4is was also reported in these studies ( 14 , 15 , 17 ). However, the results for stroke and MI varied across studies.…”

“…Subgroup analyses were performed to evaluate whether the treatment effects of study drugs differed by baseline patient characteristics, namely, age, gender, diabetes duration, histories of CVDs, HF, and CKD, and previous exposure to insulin, which have been considered in the subgroup analyses in previous studies ( 14 – 16 , 19 , 22 ). To ensure the comparability of patient characteristics between SGLT2i and DPP4i users within each subgroup stratum, the PS matching and subdistribution hazard model analyses were redone within each stratum.…”

Differences in outcomes of hospitalizations for heart failure after SGLT2 inhibitor treatment: effect modification by atherosclerotic cardiovascular disease

“…A recent study by Patorno et al using real-world data found T2D patients receiving SGLT2 inhibitors had lower risk of hHF, compared to those receiving DPP4 inhibitors, but the magnitudes of the risk differences varied between patients with established ASCVD (44%) and those without established ASCVD (54%) [ 18 ]. Similar findings came from another study using Asian population data [ 19 ]. However, a major issue with these studies was the lack of statistical examinations to test for effect modification by ASCVD on hHF risk.…”

Effects of anti-diabetes medications on cardiovascular and kidney outcomes in Asian patients with type 2 diabetes: a rapid evidence assessment and narrative synthesis

“…In the CVD-Real 2/3 observational study, SGLT2 inhibitors were associated with significantly lower risk of cardiovascular events, major kidney events and mortality compared with other oral glucose-lowering drugs in six countries, including Japan, Singapore, and South Korea in CVD-REAL 2, and in five countries, including Japan and Taiwan in CVD-REAL 3 [79,80]. Similarly, in the EMPRISE East Asia study, empagliflozin was associated with a lower risk of hospitalization for heart failure, all-cause mortality and end-stage renal disease compared with DPP-4 inhibitors in Japan, South Korea, and Taiwan [81].…”