PracticeUpdate Conference Series ISN WCN 2019

Cardiorenal Benefits of Empagliflozin Demonstrated in Proteinuric Diabetic Kidney Disease EMPA-RENAL will further elucidate benefits in a broader population.

T he beneficial effects of the SGLT2 inhibitor empagliflozin on the primary cardiorenal outcome measure used in the EMPA-REG OUTCOME trial are evident even among those with proteinuric diabetic kidney disease, as defined in the CREDENCE trial. The findings were presented in a poster at WCN 2019. Because of these pos- itive findings, the EMPA-KIDNEY study, which will evaluate the effects of empagliflozin on primary cardiorenal outcomes in a broader diabetic kidney disease population, will move forward. “So far, we have encouraging results from second- ary endpoints of large cardiovascular outcome trials with empagliflozin, canagliflozin and dapag- liflozin with respect to kidney outcomes,” presenter Christoph Wanner, MD, from the University Hospital of Würzburg in Germany told Elsevier’s PracticeUpdate . What remains to be seen is how SGLT2 inhibitors fare when kidney outcomes com- prise the primary endpoint. “With the present study,” he explained, “we evalu- ated the CREDENCE kidney primary endpoint in the EMPA-REG OUTCOME study in order to see whether a secondary endpoint will match the pri- mary endpoint when made equal.” The CREDENCE trial, which compared the effect of canagliflozin with placebo on renal and cardiovascular outcomes in the setting of proteinuric diabetic kidney disease was stopped early because of efficacy. For the EMPA-REG OUTCOME trial, 7020 adults from 42 countries with type 2 diabetes, a glycated hemoglobin (HbA1c) 7.0% to 9.0% if they were

Dr. Christoph Wanner

drug-naive and 7.0% to 10.0% if they were on stable glucose-lowering therapy, established car- diovascular disease, and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m 2 were ran- domized in a 1:1:1 fashion to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily, in addition to standard of care. Glucose-lowering therapy remained unchanged for the first 12 weeks, although glycemic rescue medication was permit- ted if the patient had a confirmed fasting glucose >240 mg/dL. Subsequently, investigators were encouraged to adjust the glucose-lowering therapy to achieve optimal glycemic control, according to local guidelines. Overall, 4.3% of patients treated with empagliflozin and 7.3% on placebo achieved the post-hoc cardio- renal outcome of end-stage kidney disease (ESKD), defined as initiation of maintenance renal replace- ment therapy or sustained eGFR <15 mL/min/1.73 m 2 , sustained doubling of serum creatinine, and renal or cardiovascular death, which translated to a 43% reduction in relative risk (hazard ratio 0.57; 95% CI 0.46–0.70). Dr. Wanner and his colleagues analyzed the outcomes based on patients’ eligibility for the CREDENCE trial, which included an eGFR ≥30 to <90mL/min/1.73m 2 and a urine albumin-to-creatinine

" SGLT2 inhibitors are effective in lower ranges of kidney function, a range which is not covered by current labels in most parts of the world. "

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PRACTICEUPDATE CONFERENCE SERIES • WCN 2019