EMPRISE: Empagliflozin Bests GLP-1 RAs, DPP-4 Inhibitors for Reducing Heart Failure Hospitalizations

Elisabetta Patorno, MD, DrPH

Data from the EMPRISE study underlines the magnitude of impact use of SGLT2 inhibitors can provide compared with other glucose-lowering therapies.

Presented at the American Diabetes Association (ADA) 82nd Scientific Sessions, the real-world comparative effectiveness and safety study placing empagliflozin against DPP-4 inhibitors and GLP-1 receptor agonists found use of empagliflozin was associated with relative risk reductions of more than 50% against DPP-4 inhibitors and nearly 40% against GLP-1 receptor agonists for hospitalizations for heart failure among patients with type 2 diabetes.

“With more than 29 million people in the U.S. diagnosed with type 2 diabetes, up to 22% of whom may also have heart failure, it is critical that healthcare professionals caring for this population have treatments that demonstrate cardiovascular effectiveness in routine care,” said co-investigator Elisabetta Patorno, MD, DrPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and associate professor of medicine, Harvard Medical School, in a statement. “These five-year results from EMPRISE, showing empagliflozin was associated with a decreased risk of hospitalization for heart failure and for death, are encouraging data for adults with type 2 diabetes and their care team.”

A 5-year monitoring program assessing the effectiveness and safety of empagliflozin using the Medicare, Optum Informatics, and IBM MarketScan databases from 2014-2019, the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) study created propensity-matched cohorts from the aforementioned databases and compared the agents for incidence of heart failure hospitalization in primary or discharge positions. The specific primary outcome of interest was incidence of heart failure hospitalization in primary (HHF-Specific) or any discharge positions (HHF-Broad), a composite of myocardial infarction (MI) and stroke, and all-cause mortality, which was only assessed in patients with Medicare claims data. The safety outcomes interest for the trial were incidence of lower-limb amputations, nonvertebral fractures, diabetic ketoacidosis (DKA), acute kidney injury (AKI), renal and bladder cancers.

When comparing empagliflozin against DPP-4 inhibitors, investigators had obtained data related to cohorts of 136,937 new empagliflozin users and 599,537 new DPP-4 inhibitor users before propensity score-matching. After propensity score-matching, investigators were left with a pair of cohorts containing 115,116 individual patients. Investigators noted these individuals were matched based on 140 baseline patient characteristics.

Upon analysis, results indicated use of empagliflozin was associated with a reduced risk of heart failure hospitalizations, with reductions observed for the HHF-Specific outcome, (HR, 0.47 [95% CI, 0.41-0.55]) and the HHF-Broad outcome (HR, 0.67 [95% CI, 0.62-0.72]), and all-cause mortality (HR, 0.56 [95% CI, 0.46-0.68]), but a similar risk of the composite of MI or stroke (HR, 0.92 [95% CI, 0.84-1.02]). When assessing safety, results indicated empagliflozin use was associated with a reduced risk of AKI (HR, 0.73 [95% CI, 0.68-0.78]), an increased risk of DKA (HR, 1.88 [95% CI, 1.51-2.34]), and a similar risk of lower-limb amputations, fractures, and renal and bladder cancers.

When comparing empagliflozin against GLP-1 receptor agonist use, after propensity-score matching, investigators obtained data related to 105,955 new users of empagliflozin and 105,955 new users of GLP-1 receptor agonists. Further matching identified initiators 72,498 pairs of new empagliflozin users and new liraglutide users.

Upon analysis, empagliflozin use was associated with a reduction in risk of had a lower risk of hospitalization for heart failure (HR, 0.62 [95% CI, 0.53-0.71]) and a similar risk of MI (HR, 0.95 [95% CI, 0.85, 1.07]), stroke (HR, 1.09 [95% CI, 0.94-1.27)], and mortality (HR, 0.91 [95% CI, 0.77-1.08]) when compared to GLP-1 receptor agonist use, with these results appearing consistent regardless of cardiovascular disease history. When comparing new empagliflozin users to new liraglutide users, investigators noted the observed trends were similar to comparisons against all GLP-1 receptor agonists.

“We are pleased to present the final data from EMPRISE in the U.S., which encompasses information from nearly 500,000 adults in a real-world care setting,” said Leonard Glass, MD, vice president of Diabetes Global Medical Affairs at Eli Lilly and Company, in the aforementioned statement. “As we strive to help fill unmet treatment needs, this study reinforces our longstanding commitment to people living with cardio-metabolic conditions. Building upon our robust clinical trial program, EMPRISE highlights the potential of Jardiance to improve health outcomes in routine clinical practice.”

These studies, “Effectiveness and Safety of Empagliflozin in Routine Care: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study,” and “Cardiovascular Effectiveness of Empagliflozin vs. Glucagon-Like Peptide-1 Receptor Agonists or Liraglutide in the EMPRISE Study,” were presented at ADA 2022.