EMPRISE reinforces CV benefits of empagliflozin

The efficacy and  cardiovascular (CV) safety of the SGLT2* inhibitor empagliflozin vs DPP-4** inhibitors and GLP-1*** receptor agonists in real-world patients were demonstrated in two interim analyses of the EMPRISE⁺ study presented at ADA 2020.

Over 5 years, EMPRISE will collect real-world evidence that is beyond the scope of cardiovascular outcomes trials (CVOTs). EMPRISE investigators will specifically assess whether the CV effectiveness of empagliflozin seen in EMPA-REG OUTCOME, the first CVOT to demonstrate cardioprotection, can be confirmed in routine clinical practice with a broader patient cohort.

CV outcomes in older adults

In one of the analyses, empagliflozin reduced the risk of hospitalization for heart failure (HHF), both as a primary diagnosis at discharge (HHF-specific) and as diagnosis of any sort at discharge (HHF-broad), vs DPP-IV inhibitors (hazard ratio [HR] for HHF-specific, 0.43, 95 percent confidence interval [CI], 0.3–0.63; HR for HHF-broad, 0.57, 95 percent CI, 0.47–0.69). [ADA 2020, abstract 133-LB]

Empagliflozin also reduced the risk for major adverse cardiovascular events (MACE; HR, 0.63, 95 percent CI, 0.5–0.79) vs DPP-IV inhibitors.

Compared with GLP-1 receptor agonists, empagliflozin reduced the risk for HHF (HR for HHF-specific, 0.67, 95 percent CI, 0.50–0.91; HR for HHF-broad, 0.83; 95 percent CI, 0.71–0.96) but conferred similar risk for MACE (HR, 1.02; 95 percent CI, 0.85-1.23).

For this analysis, researchers assessed data from the Medicare database between 2014 and 2017. The aim was to identify propensity score-matched patients who were 66 years of age with type 2 diabetes (T2D) and initiated on either empagliflozin, a DPP-4 inhibitor, or a GLP-1 receptor agonist.

“Results for the individual components of MACE were consistent and robust to competing risks,” said principal author Dr Elisabetta Patorno, assistant professor of medicine at Harvard Medical School and associate epidemiologist, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital both in Boston, Massachusetts.

“These findings, addressing the comparative effectiveness of empagliflozin in routine care patients with mean age of 72 years, complement available information from randomized controlled trials.”

Empagliflozin in routine care patients 

For the second interim analysis looking at figures from Medicare and two US commercial claims datasets from 2014 to 2017, empagliflozin reduced the risk for HF hospitalization (HR for HHF-specific, 0.46, 95 percent CI, 0.3-0.73; HR for HHF-broad, 0.63, 95 percent CI, 0.51-0.77) and all-cause mortality (HR, 0.52, 95 percent CI, 0.36-0.76) compared with DPP-IV inhibitors. [ADA 2020, abstract 134-LB]

There was no significant difference in risk for MI or stroke (HR, 0.89, 95 percent CI, 0.73-1.09).

In terms of the safety outcomes, empagliflozin conferred a decreased risk for acute kidney injury (HR, 0.64, 95 percent CI, 0.53-0.77), increased risk of hospitalization for diabetic ketoacidosis (HR, 1.56, 95 percent CI, 1-2.44), and similar risk for lower-limb amputations (HR, 0.97, 95 percent CI, 0.67-1.42), and bone fractures (HR,1.21, 95 percent CI, 0.81-1.81) over a mean follow-up of 178 days compared with DPP-IV inhibitors.

Patients were at least 18 years of age with T2D  and who were initiating either empagliflozin or a DPP-IV inhibitor. Effectiveness outcomes included HF hospitalization (defined as discharge diagnosis in the primary or any position), a composite of MI and stroke, and all-cause mortality. Safety outcomes included lower limb amputations, bone fractures, diabetic ketoacidosis, and acute kidney injury.

“In routine care, empagliflozin had an effectiveness profile consistent with randomized controlled trial findings and safety outcomes in line with documented information,” the researchers said.

The findings also provide additional context to the CVOT-generated insights into CV protection with empagliflozin.