Cardiovascular Events, Acute Hospitalizations, and Mortality in Patients With Type 2 Diabetes Mellitus Who Initiate Empagliflozin Versus Liraglutide: A Comparative Effectiveness Study

Background In cardiovascular outcome trials, the sodium glucose cotransporter 2 inhibitor empagliflozin and glucagon‐like peptide‐1 (GLP‐1) receptor agonist liraglutide caused similar reductions in major adverse cardiac events (MACE). We compared clinical outcomes in routine clinical care. Methods and Results EMPLACE (Cardiovascular and Renal Outcomes, and Mortality in Danish Patients with Type 2 Diabetes Who Initiate Empagliflozin Versus GLP‐1RA: A Danish Nationwide Comparative Effectiveness Study) is an ongoing nationwide population‐based comparative effectiveness cohort study in Denmark. For the present study, we included 14 498 new users of empagliflozin and 12 706 new users of liraglutide, 2015 to 2018. Co‐primary outcomes were expanded major adverse cardiac events (stroke, myocardial infarction, unstable angina, coronary revascularization, hospitalization for heart failure [HHF], or all‐cause death); HHF or all‐cause death; and first HHF or first initiation of loop‐diuretic therapy. Secondary outcomes included all‐cause hospitalization or death. We applied propensity score balancing and Cox regression to compute adjusted hazard ratios (aHRs) in on‐treatment (OT) and intention‐to‐treat (ITT) analyses. Cohorts were well balanced at baseline (median age 61 years, 59% men, diabetes mellitus duration 6.6 years, 30% with preexisting cardiovascular disease). During mean follow‐up of 1.1 years in OT and 1.5 years in ITT analyses, empagliflozin versus liraglutide was associated with a similar rate of expanded major adverse cardiac events (OT aHR, 1.02; 95% CI, 0.91–1.14; ITT aHR, 1.06; 95% CI, 0.96–1.17), and HHF or all‐cause death (OT aHR, 0.97; 95% CI, 0.85–1.11; ITT aHR, 1.02; 95% CI, 0.91–1.14); and a decreased rate of a first incident HHF or loop‐diuretic initiation (OT aHR, 0.80; 95% CI, 0.68–0.94; ITT aHR, 0.87; 95% CI, 0.76–1.00), and of all‐cause hospitalization or death (OT aHR, 0.93; 95% CI, 0.89–0.98; ITT aHR, 0.93; 95% CI, 0.90–0.97). Conclusions Empagliflozin and liraglutide initiators had comparable rates of expanded major adverse cardiac events, and HHF or all‐cause death, whereas empagliflozin initiators had a lower rate of a first HHF or loop‐diuretic initiation.