Empagliflozin and progression of kidney disease in type 2 diabetes

EMPA-REG OUTCOME Investigators

Research output: Contribution to journalArticle

876 Citations (Scopus)

Abstract

BACKGROUND 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. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. METHODS We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). 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%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)323-334
Number of pages12
JournalNew England Journal of Medicine
Volume375
Issue number4
DOIs
StatePublished - Jul 28 2016

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Kidney Diseases
Type 2 Diabetes Mellitus
Kidney
Placebos
Albuminuria
Renal Replacement Therapy
Creatinine
Sodium-Glucose Transport Proteins
empagliflozin
Body Surface Area
Risk Reduction Behavior
Serum
Glomerular Filtration Rate
Confidence Intervals

ASJC Scopus subject areas

  • Medicine(all)

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Empagliflozin and progression of kidney disease in type 2 diabetes. / EMPA-REG OUTCOME Investigators.

In: New England Journal of Medicine, Vol. 375, No. 4, 28.07.2016, p. 323-334.

Research output: Contribution to journalArticle

EMPA-REG OUTCOME Investigators. / Empagliflozin and progression of kidney disease in type 2 diabetes. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 4. pp. 323-334.
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abstract = "BACKGROUND 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. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. METHODS We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7{\%}) in the empagliflozin group and in 388 of 2061 (18.8{\%}) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95{\%} confidence interval, 0.53 to 0.70; P<0.001). 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{\%}. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3{\%}) in the empagliflozin group and in 14 of 2333 patients (0.6{\%}) in the placebo group, representing a 55{\%} lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. CONCLUSIONS 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.",
author = "{EMPA-REG OUTCOME Investigators} and Christoph Wanner and Inzucchi, {Silvio E.} and Lachin, {John M.} and David Fitchett and {Von Eynatten}, Maximilian and Michaela Mattheus and Johansen, {Odd Erik} and Woerle, {Hans J.} and Broedl, {Uli C.} and Bernard Zinman and D. Aizenberg and M. Ulla and J. Waitman and {De Loredo}, L. and J. Far{\'i}as and H. Fideleff and M. Lagrutta and N. Maldonado and H. Colombo and {Ferre Pacora}, F. and A. Wasserman and L. Maffei and R. Lehman and J. Selvanayagam and M. d’Emden and P. Fasching and B. Paulweber and H. Toplak and A. Luger and H. Drexel and R. Prager and C. Schnack and G. Schernthaner and E. Fliesser-G{\"o}rzer and S. Kaser and A. Scheen and {Van Gaal}, L. and G. Hollanders and Y. Kockaerts and L. Capiau and A. Chachati and A. Persu and M. Hermans and D. Vantroyen and C. Vercammen and {Van de Borne}, P. and K. Benhalima and C. Mathieu and F. Lienart and Schiff, {Eugene R}",
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T1 - Empagliflozin and progression of kidney disease in type 2 diabetes

AU - EMPA-REG OUTCOME Investigators

AU - Wanner, Christoph

AU - Inzucchi, Silvio E.

AU - Lachin, John M.

AU - Fitchett, David

AU - Von Eynatten, Maximilian

AU - Mattheus, Michaela

AU - Johansen, Odd Erik

AU - Woerle, Hans J.

AU - Broedl, Uli C.

AU - Zinman, Bernard

AU - Aizenberg, D.

AU - Ulla, M.

AU - Waitman, J.

AU - De Loredo, L.

AU - Farías, J.

AU - Fideleff, H.

AU - Lagrutta, M.

AU - Maldonado, N.

AU - Colombo, H.

AU - Ferre Pacora, F.

AU - Wasserman, A.

AU - Maffei, L.

AU - Lehman, R.

AU - Selvanayagam, J.

AU - d’Emden, M.

AU - Fasching, P.

AU - Paulweber, B.

AU - Toplak, H.

AU - Luger, A.

AU - Drexel, H.

AU - Prager, R.

AU - Schnack, C.

AU - Schernthaner, G.

AU - Fliesser-Görzer, E.

AU - Kaser, S.

AU - Scheen, A.

AU - Van Gaal, L.

AU - Hollanders, G.

AU - Kockaerts, Y.

AU - Capiau, L.

AU - Chachati, A.

AU - Persu, A.

AU - Hermans, M.

AU - Vantroyen, D.

AU - Vercammen, C.

AU - Van de Borne, P.

AU - Benhalima, K.

AU - Mathieu, C.

AU - Lienart, F.

AU - Schiff, Eugene R

PY - 2016/7/28

Y1 - 2016/7/28

N2 - BACKGROUND 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. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. METHODS We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). 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%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. CONCLUSIONS 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.

AB - BACKGROUND 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. We wanted to determine the long-term renal effects of empagliflozin, an analysis that was a prespecified component of the secondary microvascular outcome of that trial. METHODS We randomly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m 2 of body-surface area to receive either empagliflozin (at a dose of 10 mg or 25 mg) or placebo once daily. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria. RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients (12.7%) in the empagliflozin group and in 388 of 2061 (18.8%) in the placebo group (hazard ratio in the empagliflozin group, 0.61; 95% confidence interval, 0.53 to 0.70; P<0.001). 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%. Renal-replacement therapy was initiated in 13 of 4687 patients (0.3%) in the empagliflozin group and in 14 of 2333 patients (0.6%) in the placebo group, representing a 55% lower relative risk in the empagliflozin group. There was no significant between-group difference in the rate of incident albuminuria. The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population. CONCLUSIONS 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.

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DO - 10.1056/NEJMoa1515920

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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