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J Am Soc Nephrol. 2018 Nov;29(11):2755-2769. doi: 10.1681/ASN.2018010103. Epub 2018 Oct 12.

Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial.

Author information

1
Division of Nephrology, Department of Medicine, Würzburg University Clinic, Würzburg, Germany; Wanner_C@ukw.de.
2
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
3
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
4
Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
5
Division of Nephrology, Department of Medicine, Würzburg University Clinic, Würzburg, Germany.
6
Boehringer Ingelheim International GmbH, Ingelheim, Germany.
7
Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
8
Boehringer Ingelheim International GmbH, Biberach, Germany.
9
Ulm University, Ulm, Germany.
10
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
11
Abdominal Centre Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; and.
12
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.

Abstract

BACKGROUND:

Empagliflozin slowed the progression of CKD in patients with type 2 diabetes and cardiovascular disease in the EMPA-REG OUTCOME Trial. In a prespecified statistical approach, we assessed treatment differences in kidney function by analyzing slopes of eGFR changes.

METHODS:

Participants (n=7020) were randomized (1:1:1) to empagliflozin 10 mg/d, empagliflozin 25 mg/d, or placebo added to standard of care. We calculated eGFR slopes using random-intercept/random-coefficient models for prespecified study periods: treatment initiation (baseline to week 4), chronic maintenance treatment (week 4 to last value on treatment), and post-treatment (last value on treatment to follow-up).

RESULTS:

Compared with placebo, empagliflozin was associated with uniform shifts in individual eGFR slopes across all periods. On treatment initiation, adjusted mean slope (eGFR change per week, ml/min per 1.73 m2) decreased with empagliflozin (-0.77; 95% confidence interval, -0.83 to -0.71; placebo: 0.01; 95% confidence interval, -0.08 to 0.10; P<0.001). However, annual mean slope (ml/min per 1.73 m2 per year) did not decline with empagliflozin during chronic treatment (empagliflozin: 0.23; 95% confidence interval, 0.05 to 0.40; placebo: -1.46; 95% confidence interval, -1.74 to -1.17; P<0.001). After drug cessation, the adjusted mean eGFR slope (ml/min per 1.73 m2 per week) increased and mean eGFR returned toward baseline level only in the empagliflozin group (0.56; 95% confidence interval, 0.49 to 0.62; placebo -0.02; 95% confidence interval, -0.12 to 0.08; P<0.001). Results were consistent across patient subgroups at higher CKD risk.

CONCLUSIONS:

The hemodynamic effects of empagliflozin, associated with reduction in intraglomerular pressure, may contribute to long-term preservation of kidney function.

KEYWORDS:

chronic kidney disease; diabetes mellitus; randomized controlled trials

PMID:
30314978
PMCID:
PMC6218863
[Available on 2019-11-01]
DOI:
10.1681/ASN.2018010103

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