Diabetes confers an increased risk of adverse cardiovascular and renal events. In the EMPA-REG OUTCOME trial, empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events. A further analysis was undertaken to determine the long-term renal effects of empagliflozin - an analysis that was a prespecified component of the secondary microvascular outcome of that trial
Renal prespecified outcomes:
- first renal microvascular outcome was incident or worsening nephropathy, defined as progression to macroalbuminuria (urinary albuminto- creatinine ratio, >=300 mg of albumin per gram of creatinine); a doubling of the serum creatinine level, accompanied by an eGFR of .45 ml per minute per 1.73 m2, as calculated by the MDRD formula; the initiation of renal-replacement therapy; or death from renal disease
- other prespecified renal microvascular outcomes were a composite of incident or worsening nephropathy or death from cardiovascular causes, the individual components of incident or worsening nephropathy, and incident albuminuria (urinary albuminto- creatinine ratio, >=30) in patients with a normal albumin level (urinary albumin-to-creatinine ratio, <30) at baseline
- post hoc analyses
- undertaken in a subgroup of patients with prevalent kidney disease (defined as an eGFR of 59 ml per minute per 1.73 m2 or less, as calculated by the MDRD formula, or macroalbuminuria) at baseline
- post hoc analyses of a composite of a doubling of the serum creatinine level, the initiation of renal-replacement therapy, or death from renal disease.
Renal outcomes:
An assessment of renal outcomes was a prespecified objective of the trial, and outcomes were defined in a secondary statistical analysis plan
- incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 patients (18.8%) in the placebo group, a significant relative risk reduction of 39%
- composite outcome of incident or worsening nephropathy or cardiovascular death was significantly lower in the empagliflozin group than in the placebo group
- progression to macroalbuminuria occurred in 459 of 4091 patients (11.2%) in the empagliflozin group and in 330 of 2033 (16.2%) in the placebo group, a significant relative risk reduction of 38%
- a 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%
- initiation of renal-replacement therapy occurred in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 (0.6%) in the placebo group, a significant relative risk reduction of 55%
- three deaths from renal disease in the empagliflozin group (0.1%) and none in the placebo group
- no significant between-group difference in the rate of incident albuminuria, which occurred in 1430 of 2779 patients (51.5%) in the empagliflozin group and in 703 of 1374 (51.2%) in the placebo group
Study authors 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."
Reference:
Wanner C et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016