Empagliflozin Provides Greater HF Risk Reduction than Other Glucose-Lowering Agents

This article was originally published on EndocrinologyNetwork.com.

Empagliflozin provides a greater magnitude of risk reduction for heart failure hospitalizations than other glucose-lowering agents, according to data from the EMPRISE study.

A real-world comparative effectiveness and safety study comparing empagliflozin against DPP-4 inhibitors and GLP-1 receptor agonists found use of empagliflozin was associated with relative risk reductions greater than 50% against DPP-4 inhibitors and greater than 30% compared 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, of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, in a statement.

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.

“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," Patorno added.

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.