Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

Abstract

BACKGROUND:

Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies.

METHODS:

The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.

FINDINGS:

Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.

INTERPRETATION:

Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

• Authors: Avraham Karasik, Stefanie Lanzinger, Elise Chia-Hui Tan, Daisuke Yabe, Dae Jung Kim, Wayne H-H Sheu, Cheli Melzer-Cohen, Reinhard W Holl, Kyoung Hwa Ha, Kamlesh Khunti, Francesco Zaccardi, Anuradhaa Subramanian, Krishnarajah Nirantharakumar, Thomas Nyström, Leo Niskanen, Majken Linnemann Jensen, Fabian Hoti, Riho Klement, Anouk Déruaz-Luyet, Moe H Kyaw, Lisette Koeneman, Dorte Vistisen, Bendix Carstensen, Sigrun Halvorsen, Gisle Langslet, Soulmaz Fazeli Farsani, Elisabetta Patorno, Júlio Núñez, EMPRISE Europe and Asia Study Group
• Journal: Diabetes & metabolism (Diabetes Metab) Vol. 49 Issue 2 Pg. 101418 (03 2023) ISSN: 1878-1780 [Electronic] France
• PMID: 36608816 (Publication Type: Comparative Study, Journal Article, Multicenter Study)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
• empagliflozin
• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors

Topics

• Humans
• Cardiovascular Diseases (chemically induced, epidemiology, etiology)
• Cohort Studies
• Diabetes Mellitus, Type 2 (drug therapy, epidemiology)
• Dipeptidyl-Peptidase IV Inhibitors (adverse effects, therapeutic use)
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (therapeutic use)
• Europe (epidemiology)
• Heart Failure (chemically induced, epidemiology, etiology)
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Kidney (drug effects)
• Myocardial Infarction (chemically induced, epidemiology, etiology)
• Sodium-Glucose Transporter 2 Inhibitors (adverse effects, therapeutic use)
• Stroke (chemically induced, epidemiology, etiology)
• Kidney Diseases (chemically induced, epidemiology, etiology)
• Asia (epidemiology)