Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study

Cardiovasc Diabetol. 2024 Feb 8;23(1):57. doi: 10.1186/s12933-024-02150-0.

Abstract

Background: No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovascular risk. We reported the final-year results of the EMPRISE study, a monitoring program designed to evaluate the cardiorenal effectiveness of empagliflozin across broad patient subgroups.

Methods: We identified patients ≥ 18 years old with type 2 diabetes who initiated empagliflozin or GLP-1RA from 2014 to 2019 using US Medicare and commercial claims databases. After 1:1 propensity score matching using 143 baseline characteristics, we evaluated risks of outcomes including myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE - MI, stroke, or cardiovascular mortality), a composite of HHF or cardiovascular mortality, and progression to end-stage kidney disease (ESKD) (in patients with chronic kidney disease stages 3-4). We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years, overall and within subgroups of age, sex, baseline atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF).

Results: We identified 141,541 matched pairs. Compared with GLP-1RA, empagliflozin was associated with similar risks of MI or stroke [HR: 0.99 (0.92, 1.07); RD: -0.23 (-1.25, 0.79)], and lower risks of HHF [HR: 0.50 (0.44, 0.56); RD: -2.28 (-2.98, -1.59)], MACE [HR: 0.90 (0.82, 0.99); RD: -2.54 (-4.76, -0.32)], cardiovascular mortality or HHF [HR: 0.77 (0.69, 0.86); RD: -4.11 (-5.95, -2.29)], and ESKD [0.75 (0.60, 0.94); RD: -6.77 (-11.97, -1.61)]. Absolute risk reductions were larger in older patients and in those with baseline ASCVD/HF. They did not differ by sex.

Conclusions: The cardiovascular benefits of empagliflozin vs. cardioprotective GLP-1RA agents were larger in older patients and in patients with history of ASCVD or HF, while they did not differ by sex. In patients with advanced CKD, empagliflozin was associated with risk reductions of progression to ESKD.

Keywords: Cardiovascular disease; Chronic kidney disease; Effectiveness; Empagliflozin; GLP-1RA; SGLT2i; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Aged
  • Atherosclerosis* / drug therapy
  • Benzhydryl Compounds*
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Glucosides*
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Medicare
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Stroke* / diagnosis
  • Stroke* / epidemiology
  • Stroke* / prevention & control
  • United States

Substances

  • empagliflozin
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Benzhydryl Compounds
  • Glucosides