In a prespecified subanalysis of EMPA-REG, the authors assessed the effect of empagliflozin on incident or worsening nephropathy. Among the 6185 participants, all of whom began the trial with an eGFR of ≥30 mL/min/1.73 m2, incident or worsening nephropathy occurred in 12.7% of empagliflozin recipients and 18.8% of placebo recipients (hazard ratio, 0.61; 95% confidence interval, 0.53–0.70). Doubling of serum creatinine levels was significantly less common in the empagliflozin group (1.5% vs. 2.6%; relative risk reduction, 44%), as was initiation of renal replacement therapy (0.3% vs. 0.6%; relative risk reduction, 55%). There was no significant between-group difference in the rate of incident albuminuria.
There was much discussion about the potential mechanisms behind these effects at the American Diabetes Association’s 76th Scientific Sessions, where these data were first presented. The authors propose that, in addition to its haemodynamic effects, empagliflozin may reduce glomerular hypertension through reductions in proximal tubule sodium reabsorption; however, more work will be required to support any hypotheses.
The authors also point out that, as most of the study cohort were also treated with RAAS blockers (the recommended treatment for kidney disease) owing to their high cardiovascular risk, it is not possible to generalise these findings to other people with type 2 diabetes at lower cardiovascular risk.
These findings can be read in the New England Journal of Medicine here.