EMPRISE: Early Data Show Empagliflozin Beats DPP-4s in CV Events, but Cost of Care Is Similar

When doctors decide which therapy to prescribe for a patient with type 2 diabetes (T2D), they typically have results from placebo-controlled trials for each drug. Less common are studies comparing drugs against each other. The EMPRISE study aims to fill this gap by evaluating the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin against drugs in the DPP-4 inhibitor class, using real-world data.

So far, early data from EMPRISE presented at the 79th Scientific Sessions of the American Diabetes Association in San Francisco, California, show that empagliflozin is associated with fewer cardiovascular (CV) events than DPP-4 inhibitors—but patients’ overall healthcare costs are about the same.

The study is funded by Boehringer Ingelheim, which markets empagliflozin as Jardiance with Eli Lilly.

Elisabetta Patorno, MD, DrPH, of Brigham & Women’s Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics, presented early cardiovascular and safety results from EMPRISE in an oral session Monday. She explained that EMPRISE uses data from the Optum and MarketScan databases as well as Medicare, and will cover the first 5 years of US empagliflozin use, from August 2014 to September 2019.

Investigators ultimately expect to capture data from up to 232,000 patients. All will be at least 18 years old and starting either empagliflozin or a DPP-4 inhibitor without having taken either drug in the past year, Patorno said.

Data presented covered 2014 to 2016, and included 17,551 matched pairs of empagliflozin and DPP-4 inhibitor users. Patients’ average age was 58.7 years and nearly 25% in each group had a history of CV disease.

Earlier this year, Boehringer Ingelheim announced that the early results of EMPRISE showed that starting empagliflozin was associated with a 22% relative risk reduction in all-cause hospitalizations, relative to DPP-4 inhibitors. The results Patorno presented Monday showed:

• Empagliflozin was associated with a lower risk of a composite CV outcome (myocardial infarction, stroke, all-cause mortality). The hazard ratio (HR) was 0.82 (95% CI, 0.62-1.10).
• Empagliflozin was also associated with a lower risk of an extended CV outcome, which included the composite plus heart failure hospitalization or coronary revascularization; the HR was 0.73 (95% CI, 0.60-0.88). By itself, the risk of heart failure hospitalization is substantially less likely with empagliflozin; HR was 0.56 (95% CI, 0.43-0.73).
• Safety measures of note included the risk of hospitalization for diabetic ketoacidosis, which favored the DPP-4 inhibitors. The HR for empagliflozin was 1.74 (95% CI, 0.84-3.58). Empagliflozin also had a higher risk of lower limb amputations, although the raw numbers were small (17 for empagliflozin vs 13 for DPP-4 inhibitors); HR 1.20 (95% CI, 0.57-2.53).
• Empagliflozin offered far lower risk of acute kidney injury that required dialysis, which is consistent with findings presented through the 2019 ADA sessions that show the SGLT2 class offer early protection against renal decline. The HR was 0.64 (95% CI, 0.43-0.95).

In her presentation, Patorno noted that the findings so far are consistent the benefits and risks seen in the EMPA-REG OUTCOME study, the first to demonstrate CV benefits in a T2D therapy. A post-hoc analysis from EMPA-REG OUTCOME presented Monday showed empagliflozin reduces cardiovascular and renal risk in adult patients with T2D who have known cardiovascular disease as well as a form of chronic kidney disease (CKD) without high levels of protein in the urine, known as over proteinuria.²

"The results support the need for additional studies aimed at addressing important unmet medical needs for people with various forms of kidney disease,” Mohamed Eid, MD, MPH, MHA, vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, said in a statement. “To that end, we have initiated an outcomes trial, EMPA-KIDNEY, to investigate the effects of empagliflozin on cardiovascular death and the progression of kidney disease in a broad population of adults with chronic kidney disease."

Total Cost of Care Similar

While the clinical data from EMPRISE presented Monday gave empagliflozin an edge on CV results, a separate abstract from the study showed that the total cost of care among patients who started the SGLT2 inhibitor finds that so far, the cost of these patients to the health system is about the same as those taking DPP-4 inhibitors.³

While patients taking empagliflozin had lower medical costs, this was offset by higher pharmacy costs:

• Total cost of care, per member per year (PMPY) for empagliflozin was $17,771, compared with $17,814 for DPP-4 inhibitors, for a difference of $43.
• Medical costs PMPY (inpatient and outpatient) were lower for empagliflozin at $8932; for DPP-4 inhibitors PMPY medical costs were $9729.
• Pharmacy costs PMPY were higher for empagliflozin at $8772; for DPP-4 inhibitors, pharmacy PMPY costs were $7990.
• All cardiovascular related medical costs were lower for those taking empagliflozin. The SGLT2 inhibitor was the first T2D therapy shown to produce cardiovascular benefits in the EMPA-REG OUTCOME trial.

References

1. Patorno E, Pawar A, Franklin J et al. Empagliflozin selected cardiovascular and safety outcomes in routine care: first results from the empagliflozin comparative effectiveness and safety (EMPRISE) study. Presented at: 79^th Scientific Sessions of the American Diabetes Association, San Francisco, California; June 7-12, 2019; Abstract number 249-OR. doi.org/10.2337/db19-249-OR.
2. Inzucchi S, Zinman B, George J, et al. Empagliflozin and cardiorenal outcomes in patients with nonproteinuric kidney disease in the EMPA-REG OUTCOME trial. Presented at: 79^th Scientific Sessions of the American Diabetes Association, San Francisco, California; June 7-12, 2019; Abstract number 248-OR. doi.org/10.2337/db19-248-OR.
3. Health care costs and medication burden in routine care initiators of empagliflozin: a first analysis from the empagliflozin comparative effectiveness and safety (EMPRISE) study. Presented at: 79^th Scientific Sessions of the American Diabetes Association, San Francisco, California; June 7-12, 2019; Abstract number 1193-P. doi.org/10.2337/db19-1193-P.