Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes

EMPA-REG OUTCOME Investigators

Research output: Contribution to journalArticle

3473 Citations (Scopus)

Abstract

BACKGROUND The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.

Original languageEnglish (US)
Pages (from-to)2117-2128
Number of pages12
JournalNew England Journal of Medicine
Volume373
Issue number22
DOIs
StatePublished - Nov 26 2015
Externally publishedYes

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Type 2 Diabetes Mellitus
Mortality
Placebos
Cause of Death
Risk Reduction Behavior
Hospitalization
Sodium-Glucose Transport Proteins
Stroke
Myocardial Infarction
empagliflozin
Unstable Angina
Heart Failure
Observation
Confidence Intervals
Morbidity
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. / EMPA-REG OUTCOME Investigators.

In: New England Journal of Medicine, Vol. 373, No. 22, 26.11.2015, p. 2117-2128.

Research output: Contribution to journalArticle

EMPA-REG OUTCOME Investigators. / Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. In: New England Journal of Medicine. 2015 ; Vol. 373, No. 22. pp. 2117-2128.
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abstract = "BACKGROUND The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5{\%}) in the pooled empagliflozin group and in 282 of 2333 patients (12.1{\%}) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02{\%} confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7{\%}, vs. 5.9{\%} in the placebo group; 38{\%} relative risk reduction), hospitalization for heart failure (2.7{\%} and 4.1{\%}, respectively; 35{\%} relative risk reduction), and death from any cause (5.7{\%} and 8.3{\%}, respectively; 32{\%} relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.",
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T1 - Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes

AU - EMPA-REG OUTCOME Investigators

AU - Zinman, Bernard

AU - Wanner, Christoph

AU - Lachin, John M.

AU - Fitchett, David

AU - Bluhmki, Erich

AU - Hantel, Stefan

AU - Mattheus, Michaela

AU - Devins, Theresa

AU - Johansen, Odd Erik

AU - Woerle, Hans J.

AU - Broedl, Uli C.

AU - Inzucchi, Silvio E.

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 - Pandey, A.

PY - 2015/11/26

Y1 - 2015/11/26

N2 - BACKGROUND The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.

AB - BACKGROUND The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care.

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