EMPRISE shows CV efficacy, safety of empagliflozin in routine care

The final analysis of the 5-year monitoring EMPRISE* programme presented at ADA 2022 demonstrated the cardiovascular (CV) efficacy of empagliflozin in patients with type 2 diabetes (T2D), with a safety profile that aligns with existing evidence.

Using real-world data from Medicare and two US commercial claims accrued for a period of 5 years, the researchers identified >230,000** propensity-score-matched T2D patients (mean age 62 years, 55 percent male) who were initiated on either empagliflozin or a dipeptidyl peptidase-4 inhibitor (DPP-4i). A third of patients had a history of CV disease*** (CVD). Participants were followed for hospitalization for heart failure (HHF), HHF in any discharge position (HHF-any dx), a composite of MI and stroke, and all-cause mortality. [ADA 2022, abstract 1079-P]

After adjusting for covariates, over a mean follow-up of 8.3 months, empagliflozin was associated with a reduced risk of HHF (hazard ratio [HR], 0.50, 95 percent confidence interval [CI], 0.44–0.56) and HHF-any dx (HR, 0.71, 95 percent CI, 0.67–0.75) compared with DPP-4is. These findings corresponded to 5.4 (HFF) and 10.8 (HHF-any dx) fewer events/1,000 person-years (PY).

There was also a slight reduction in the risk of the composite outcome of MI or stroke with empagliflozin vs DPP-4is (–2.2 rate difference [RD]/1,000 PY; HR, 0.88, 95 percent CI, 0.81–0.96).

The risk of all-cause mortality was also lower with empagliflozin vs DPP-4is in a subset of patients from Medicare (–8.15 RD/1,000 PY; HR, 0.60, 95 percent CI, 0.53–0.68).

“[The] results were consistent in subgroup analyses by history of CVD, though the absolute CV benefit of empagliflozin was greater in patients with history of CVD compared with those without it,” said study investigator Dr Phyo Than Htoo from the Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, US, and colleagues.

The findings also correlate with results from the EMPA-REG OUTCOME trial, which demonstrated reduced risks of HHF (by 35 percent) and all-cause mortality (by 32 percent) with empagliflozin in T2D patients with established CVD. [Circulation 2019;139:1384-1395]

Safety

There was a reduced risk of acute kidney injury with empagliflozin relative to DPP-4is (HR, 0.71, 95 percent CI, 0.67–0.76). There were similar risks of lower limb amputations (HR, 1.07, 95 percent CI, 0.89–1.28), nonvertebral fractures (HR, 1.08, 95 percent CI, 0.92–1.26), and renal (HR, 1.00, 95 percent CI, 0.70–1.43) and bladder cancers (HR, 1.03, 95 percent CI, 0.72–1.49) between the two arms.

While there was an increased risk of hospitalization for diabetic ketoacidosis with empagliflozin (HR, 1.78, 95 percent CI, 1.44–2.19), the researchers noted that this was in line with documented safety information.

“[Taken together, our findings] complement CV outcome trial data and reinforce the … beneficial effects of empagliflozin on CV outcomes, particularly HF, regardless of baseline history of CVDs,” said the researchers.