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

Diabetes Metab. 2023 Mar;49(2):101418. doi: 10.1016/j.diabet.2022.101418. Epub 2023 Jan 3.


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.

Keywords: All-cause mortality; Cardiovascular diseases; Comparative effectiveness; Dipeptidyl peptidase-4 inhibitors; Empagliflozin; Heart failure; Meta-analysis; Observational study; Pharmacoepidemiology; Sodium-glucose transporter 2 inhibitors.

MeSH terms

  • Cardiovascular Diseases*
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / therapeutic use
  • Europe
  • Heart Failure* / complications
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney
  • Myocardial Infarction* / complications
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Stroke* / complications


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