Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
- PMID: 26378978
- DOI: 10.1056/NEJMoa1504720
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
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. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.).
Comment in
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Understanding EMPA-REG OUTCOME.Lancet Diabetes Endocrinol. 2015 Dec;3(12):928-9. doi: 10.1016/S2213-8587(15)00424-6. Lancet Diabetes Endocrinol. 2015. PMID: 26590679 No abstract available.
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Understanding EMPA-REG OUTCOME.Lancet Diabetes Endocrinol. 2015 Dec;3(12):929-30. doi: 10.1016/S2213-8587(15)00426-X. Lancet Diabetes Endocrinol. 2015. PMID: 26590680 No abstract available.
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Understanding EMPA-REG OUTCOME.Lancet Diabetes Endocrinol. 2015 Dec;3(12):930-1. doi: 10.1016/S2213-8587(15)00427-1. Lancet Diabetes Endocrinol. 2015. PMID: 26590681 No abstract available.
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Preventing cardiovascular events with empagliflozin: at what cost?Lancet Diabetes Endocrinol. 2015 Dec;3(12):931. doi: 10.1016/S2213-8587(15)00439-8. Lancet Diabetes Endocrinol. 2015. PMID: 26590682 No abstract available.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med. 2016 Mar 17;374(11):1094. doi: 10.1056/NEJMc1600827. N Engl J Med. 2016. PMID: 26981940 No abstract available.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med. 2016 Mar 17;374(11):1092. doi: 10.1056/NEJMc1600827. N Engl J Med. 2016. PMID: 26981941 No abstract available.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med. 2016 Mar 17;374(11):1092-3. doi: 10.1056/NEJMc1600827. N Engl J Med. 2016. PMID: 26981942 No abstract available.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med. 2016 Mar 17;374(11):1093. doi: 10.1056/NEJMc1600827. N Engl J Med. 2016. PMID: 26981943 No abstract available.
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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.N Engl J Med. 2016 Mar 17;374(11):1093-4. doi: 10.1056/NEJMc1600827. N Engl J Med. 2016. PMID: 26981944 No abstract available.
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No Need to Sugarcoat the Message: Is Cardiovascular Risk Reduction From SGLT2 Inhibition Related to Natriuresis?Am J Kidney Dis. 2016 Sep;68(3):349-52. doi: 10.1053/j.ajkd.2016.03.410. Epub 2016 Mar 30. Am J Kidney Dis. 2016. PMID: 27039253 No abstract available.
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Empagliflozin's Fuel Hypothesis: Not so Soon.Cell Metab. 2016 Aug 9;24(2):200-2. doi: 10.1016/j.cmet.2016.07.018. Cell Metab. 2016. PMID: 27508868
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Sodium-glucose co-transporter-2 inhibitors and cardiovascular outcome studies in people with type 2 diabetes: From efficacy to effectiveness.Diabetes Obes Metab. 2018 Apr;20(4):763-765. doi: 10.1111/dom.13142. Epub 2017 Nov 22. Diabetes Obes Metab. 2018. PMID: 29077267 No abstract available.
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