In Depth: 76th ADA Scientific Sessions
Study announces a new benefit in addition to reductions in major adverse cardiovascular events.
The takeaway from this study is that the use of empagliflozin in patients with diabetes at increased risk for cardiovascular disease may protect their kidneys. The EMPA-REG OUTCOME trial found that the addition of empagliflozin to standard of care significantly reduced risk of cardiovascular (CV) death, hospitalization for heart failure, and death from any cause vs placebo in patients with type 2 diabetes mellitus (T2DM) at high risk for CV events.
The purpose of the trial was to determine the long-term renal effects of empagliflozin, an analysis that was a pre-specified component of the secondary microvascular outcome of that trial.
Patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area were randomly assigned to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria.
The results showed that incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). Doubling of the serum creatinine level occurred in 70 of 4645 patients (1.5%) in the empagliflozin group and in 60 of 2323 (2.6%) in the placebo group, a significant relative risk reduction of 44%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population.
So from the results it was concluded that, in patients with type 2 diabetes at high cardiovascular risk, empagliflozin was associated with slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care.
The trial’s limitations included that the renal effects of empagliflozin cannot necessarily be generalized to patients with type 2 diabetes at lower cardiovascular risk, or to black patients due to the small sample size.
What makes this information important is that kidney disease develops in approximately 35% of patients with type 2 diabetes and is associated with increased mortality.
- Incident or worsening nephropathy occurred in 12.7% of 4124 patients in the empagliflozin group and in 18.8% of 2061 in the placebo group (HR, 0.61; 95% CI, 0.53-0.70; P<.001).
- Renal-replacement therapy was initiated in 0.3% in the empagliflozin group and in 0.6% in the placebo group, representing a 55% lower relative risk with empagliflozin.
- There were no significant between-group differences in the rate of incident albuminuria and the adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population.
N Engl J Med. 2016 Jun 14. [Epub ahead of print]