TY - JOUR

T1 - Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease

AU - EMPA-REG OUTCOME Trial

AU - Wanner, Christoph

AU - Lachin, John M.

AU - Inzucchi, Silvio E.

AU - Fitchett, David

AU - Mattheus, Michaela

AU - George, Jyothis

AU - Woerle, Hans J.

AU - Broedl, Uli C.

AU - von Eynatten, Maximilian

AU - Zinman, Bernard

AU - Aizenberg, D.

AU - Ulla, M.

AU - Waitman, J.

AU - De Loredo, L.

AU - Farias, 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 - Tiburcio, A.

AU - Gupta, S.

AU - Park, S.

AU - Kim, Y.

AU - Yang, J.

AU - Kim, D.

AU - Lee, S.

AU - Petrov, A.

AU - Nikolaev, K.

AU - Potemkin, V.

AU - Bystrova, A.

AU - Tarasov, N.

AU - Obrezan, A.

AU - Khokhlov, A.

AU - Huang, C.

AU - Chen, J.

AU - Wang, J.

AU - Zotov, S.

PY - 2018/1/9

Y1 - 2018/1/9

N2 - BACKGROUND: Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease in the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.METHODS: Patients with type 2 diabetes mellitus, established cardiovascular disease, and estimated glomerular filtration rate (eGFR) >= 30 mL.min(-1).1.73 m(-2) at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. We analyzed cardiovascular death, hospitalization for heart failure, all-cause hospitalization, and all-cause mortality in patients with prevalent kidney disease (defined as eGFR < 60 mL.min(-1).1.73 m(-2) and/o r urine albumin-creatinine ratio > 300 mg/g) at baseline. Additional analyses were performed in subgroups by baseline eGFR (< 45, 45-< 60, 60-= 90 mL.min(-1).1.73 m(-2)) and baseline urine albumin-creatinine ratio (> 300, 30-RESULTS: Of 7020 patients treated, 2250 patients had prevalent kidney disease at baseline, of whom 67% had a diagnosis of type 2 diabetes mellitus for > 10 years, 58% were receiving insulin, and 84% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In patients with prevalent kidney disease at baseline, empagliflozin reduced the risk of cardiovascular death by 29% compared with placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98), the risk of all-cause mortality by 24% (HR, 0.76; 95% CI, 0.59-0.99), the risk of hospitalization for heart failure by 39% (HR, 0.61; 95% CI, 0.42-0.87), and the risk of all-cause hospitalization by 19% (HR, 0.81; 95% CI, 0.72-0.92). Effects of empagliflozin on these outcomes were consistent across categories of eGFR and urine albumin-creatinine ratio at baseline and across the 2 doses studied. The adverse event profile of empagliflozin in patients with eGFR < 60 mL.min-1.1.73 m-2 was consistent with the overall trial population.CONCLUSIONS: Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.

AB - BACKGROUND: Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus and established cardiovascular disease in the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients). Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.METHODS: Patients with type 2 diabetes mellitus, established cardiovascular disease, and estimated glomerular filtration rate (eGFR) >= 30 mL.min(-1).1.73 m(-2) at screening were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily in addition to standard of care. We analyzed cardiovascular death, hospitalization for heart failure, all-cause hospitalization, and all-cause mortality in patients with prevalent kidney disease (defined as eGFR < 60 mL.min(-1).1.73 m(-2) and/o r urine albumin-creatinine ratio > 300 mg/g) at baseline. Additional analyses were performed in subgroups by baseline eGFR (< 45, 45-< 60, 60-= 90 mL.min(-1).1.73 m(-2)) and baseline urine albumin-creatinine ratio (> 300, 30-RESULTS: Of 7020 patients treated, 2250 patients had prevalent kidney disease at baseline, of whom 67% had a diagnosis of type 2 diabetes mellitus for > 10 years, 58% were receiving insulin, and 84% were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In patients with prevalent kidney disease at baseline, empagliflozin reduced the risk of cardiovascular death by 29% compared with placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.98), the risk of all-cause mortality by 24% (HR, 0.76; 95% CI, 0.59-0.99), the risk of hospitalization for heart failure by 39% (HR, 0.61; 95% CI, 0.42-0.87), and the risk of all-cause hospitalization by 19% (HR, 0.81; 95% CI, 0.72-0.92). Effects of empagliflozin on these outcomes were consistent across categories of eGFR and urine albumin-creatinine ratio at baseline and across the 2 doses studied. The adverse event profile of empagliflozin in patients with eGFR < 60 mL.min-1.1.73 m-2 was consistent with the overall trial population.CONCLUSIONS: Empagliflozin improved clinical outcomes and reduced mortality in vulnerable patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease.

KW - diabetes mellitus, type 2

KW - hospitalization

KW - kidney diseases

KW - mortality

KW - sodium-glucose transporter 2

KW - treatment outcome

KW - SGLT2 INHIBITION

KW - HEART-FAILURE

KW - RISK

KW - DEATH

KW - HOSPITALIZATION

KW - PROGRESSION

KW - MECHANISMS

KW - MORTALITY

KW - EVENTS

KW - IMPACT

U2 - 10.1161/CIRCULATIONAHA.117.028268

DO - 10.1161/CIRCULATIONAHA.117.028268

M3 - статья

VL - 137

SP - 119

EP - 129

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 2

ER -