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Kidney Week

Abstract: FR-PO227

Short-Term Changes in Albuminuria and Risk of Cardiovascular Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the EMPA-REG OUTCOME Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


  • Xie, Di, University Medical Center Groningen, Groningen, Netherlands
  • Waijer, Simke W., University Medical Center Groningen, Groningen, Netherlands
  • von Eynatten, Maximilian, Boehringer Ingelheim International GmbH, Ingelheim, Germany
  • Koitka-Weber, Audrey, Boehringer Ingelheim International GmbH, Ingelheim, Germany
  • Inzucchi, Silvio E., Yale University School of Medicine, New Haven, Connecticut, United States
  • Zinman, Bernard, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  • Wanner, Christoph, Wurzburg University Clinic, Wurzburg, Germany
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Previous studies, primarily with RAAS inhibitors, have demonstrated that a reduction in albuminuria (UACR) during the first months of treatment is associated with improved long-term cardiovascular (CV) outcomes. Whether an early reduction in UACR with SGLT2 inhibition is also a positive indicator of long-term CV benefit is unknown. We therefore assessed the association between changes in UACR over the first 12 weeks of treatment with empagliflozin or placebo and subsequent long-term CV risk in a post-hoc analysis from the EMPA-REG OUTCOME trial.


We calculated UACR change as the percentage difference from baseline to week 12 in 6820 participants who did not experience a CV outcome during the first 12 weeks. Cox regression models were used to estimate the hazard ratio (HR) for the primary MACE outcome (non-fatal MI, non-fatal stroke, CV death) and CV death or hospitalization for heart failure (CVD/HHF) for each 30% reduction in UACR after adjustment for treatment assignment, laboratory measurements and medication use.


Empagliflozin compared to placebo reduced UACR by 18% (95%CI 14-22%), and increased the likelihood of a ≥30% reduction in UACR at week 12 compared to placebo (odds ratio 1.42 [95%CI 1.27-1.58]). Over a median follow-up of 3.0 years, 704 (10.3%) primary CV and 440 (6.5%) CVD/HHF outcomes were observed. Each 30% reduction in UACR during the first 12 weeks was independently associated with an average 5% lower hazard for the MACE outcome (HR 0.95; 95%CI 0.91–0.98, p=0.002), and 8% lower hazard for the CVD/HHF outcome (HR 0.92; 95%CI 0.88–0.96, p<0.001). Results were consistent in subgroups by baseline characteristics or medication use, or empagliflozin/placebo treatment assignment(Figure).


Short-term reduction in UACR was more common with empagliflozin and was independently associated with a decreased risk of long-term CV outcomes. These results suggest that a change in albuminuria is a prognostic marker for CV outcomes.


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