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

J Am Heart Assoc. 2020 Sep 15;9(18):e016976. doi: 10.1161/JAHA.120.016976. Epub 2020 Sep 6.


Background Early reduction in albuminuria with an SGLT2 (sodium-glucose cotransporter 2) inhibitor may be a positive indicator of long-term cardiovascular and renal benefits. We assessed changes in albuminuria during the first 12 weeks of treatment and subsequent long-term cardiovascular and renal risks associated with the SGLT2 inhibitor, empagliflozin, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 diabetes Mellitus Patients) trial. Methods and Results We calculated the percentage urinary albumin creatinine ratio (UACR) change from baseline to week 12 in 6820 participants who did not experience a cardiovascular outcome (including 3-point major cardiovascular events and cardiovascular death or hospitalization for heart failure) or renal outcome (defined as 40% decline in estimated glomerular filtration rate from baseline, estimated glomerular filtration rate <15 mL/min per 1.73 m2, need for continuous renal-replacement therapy, or renal death) during the first 12 weeks. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for each 30% reduction in UACR with outcomes. Empagliflozin reduced UACR by 18% (95% CI, 14-22) at week 12 compared with placebo, and increased the likelihood of a >30% reduction in UACR (odds ratio, 1.42; 95% CI, 1.27-1.58; P<0.001). During 3.0 years of follow-up, 704 major cardiovascular events, 440 cardiovascular deaths/hospitalizations for heart failure, and 168 renal outcomes were observed. Each 30% decrease in UACR during the first 12 weeks was statistically significantly associated with a lower hazard for major cardiovascular events (HR, 0.96; 95% CI, 0.93-0.99; P=0.012), cardiovascular deaths/hospitalizations for heart failure (HR, 0.94; 95% CI, 0.91-0.98; P=0.003), and renal outcomes (HR, 0.83; 95% CI, 0.78-0.89; P<0.001). Conclusions Short-term reduction in UACR was more common with empagliflozin and was statistically significantly associated with a decreased risk of long-term cardiovascular and renal outcomes. Registration URL: Unique identifier: NCT01131676.

Keywords: cardiovascular outcomes; empagliflozin; kidney (diabetes); sodium‐glucose cotransporter 2 inhibitors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / drug therapy*
  • Albuminuria / etiology
  • Benzhydryl Compounds / therapeutic use*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Glucosides / therapeutic use*
  • Humans
  • Kidney Diseases / etiology
  • Kidney Diseases / prevention & control*
  • Male
  • Middle Aged
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome


  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin

Associated data