SAN DIEGO – Empagliflozin used in conjunction with standard of care significantly improved renal outcomes in adults with type 2 diabetes, results from a large randomized trial showed.
“These benefits were consistent among patients with and without chronic kidney disease at baseline,” Dr. Christoph Wanner said at the annual meeting of the American Society of Nephrology.
Previous studies have demonstrated that in patients with type 2 diabetes, empagliflozin, an inhibitor of the sodium glucose cotransporter 2 in the kidney, leads to significant reductions in hemoglobin A1c, weight loss, and reductions in blood pressure without increases in heart rate. Developed by Boehringer Ingelheim and Eli Lilly, the drug was approved in 2014 for the treatment of type 2 diabetes in adults. At the meeting Dr. Wanner presented new finding results from the EMPA-REG OUTCOME trial, which was published in September 2015. That study found that patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, compared with placebo, had a lower rate of the primary composite cardiovascular outcome and death from any cause when the study drug was added to standard care.
For the current analysis, the researchers evaluated renal outcomes in the study participants, which consisted of new-onset or worsening nephropathy, including new onset of macroalbuminuria (defined as a urine albumin to creatinine ratio (UACR) of greater than 300 mg/g); doubling of serum creatinine accompanied by an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73m2 or less; initiation of renal replacement therapy; or death due to renal disease. There was also a composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease.
The EMPA-REG OUTCOME trial included 2,333 patients in the placebo group and 4,687 in the empagliflozin group who were followed for a median observation time of 3.1 years. The mean age of the study participants was 63 years and 71% were male. Compared with patients in the placebo group, those in the empagliflozin group demonstrated a 39% reduction in new-onset or worsening of nephropathy (hazard ratio, 0.61; P less than .0001). The reduction “started very early,” said Dr. Wanner, who is professor of medicine and head of nephrology at University Hospital of Wurzburg, Germany. “After 3 months you see the curves [between the placebo and treatment groups] separating.”
The impact on empagliflozin on the composite outcome of doubling of serum creatinine, initiation of renal replacement therapy, or death due to renal disease was even more profound. Compared with patients in the placebo group, those in the empagliflozin demonstrated a 46% reduced risk in the composite outcome (HR, 0.54; P = .0002).
Dr. Wanner went on to present cardiovascular outcomes in patients with chronic kidney disease (CKD). Among those with an eGFR of less than 60 mL/min/1.73m2 at baseline, the primary outcome of three-point major adverse cardiac events occurred in 176 of 1,212 patients in the empagliflozin group (15%), compared with 99 of 607 patients in the placebo group (16%; HR, 0.88). Among those with an eGFR of 60 mL/min/1.73m2 or greater at baseline, the primary outcome of three-point major adverse cardiac events occurred in 314 of 3,473 patients in the empagliflozin group (9%), compared with 183 of 1,726 (11%) patients in the placebo group (HR, 0.84). At the same time, the outcome of cardiovascular death occurred in 75 of 1,212 patients in the empagliflozin group (6%), compared with 48 of 607 patients in the placebo group (8%; HR, 0.78). Among those with an eGFR of 60 mL/min/1.73m2 or greater at baseline, cardiovascular death occurred in 97 of 3,473 patients in the empagliflozin group (3%), compared with 89 of 1,726 patients in the placebo group (5%; HR, 0.53). However, there was no detectable benefit for the study medication in reducing the myocardial infarction or stroke in patients with CKD.
Among those with an eGFR of less than 60 mL/min/1.73m2 at baseline, hospitalization for heart failure occurred in 51 of 1,212 patients in the empagliflozin group (4%), compared with 43 of 607 patients in the placebo group (7%; HR, 0.59). Among those with an eGFR of 60 mL/min/1.73m2 or greater at baseline, hospitalization for heart failure occurred in 75 of 3,473 patients in the empagliflozin group (2%), compared with 52 of 1,726 patients in the placebo group (3%; HR, 0.70). At the same time, all-cause mortality occurred in 115 of 1,212 patients in the empagliflozin group (9%), compared with 72 of 607 patients in the placebo group (12%; HR, 0.80). Among those with an eGFR of 60 mL/min/1.73m2 or greater at baseline, hospitalization for heart failure occurred in 154 of 3,473 patients in the empagliflozin group (4%), compared with 122 of 1,726 patients in the placebo group (7%; HR, 0.62).