The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial and Its Clinical Impact on Patterns of Prescription for Anti-Diabetes Medication

Hyuk-Sang Kwon

doi:10.4093/jkd.2016.17.4.225

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Kwon: The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial and Its Clinical Impact on Patterns of Prescription for Anti-Diabetes Medication

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J Korean Diabetes 2016;17(4):225-232.

Published online: 10 January 2016

DOI: https://doi.org/10.4093/jkd.2016.17.4.225

The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial and Its Clinical Impact on Patterns of Prescription for Anti-Diabetes Medication

Hyuk-Sang Kwon

Division of Endocrinology, Department of Internal Medicine, Yeouido St. Mary's Hospital School of Medicine, The Catholic University of Korea, Seoul, Korea

Corresponding author: Hyuk-Sang Kwon Division of Endocrinology, Department of Internal Medicine, Yeouido St. Mary's Hospital School of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea, E-mail: drkwon@catholic.ac.kr

Received 15 November 2016 Accepted 21 November 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Since 2008, the Food and Drug Administration has required cardiovascular (CV) safety trials for all anti-diabetic medications available in the USA. Thus, new agents like dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists have been tested in CV safety trials. The results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) were released last year. Of the sodium-glucose cotransporter 2 (SGLT2) inhibitors tested, empagliflozin demonstrated a CV benefit in this trial. Another study of the renal protective effects of empagliflozin was released this year. The mechanisms supporting the cardio- and renoprotective effects of empagliflozin remain controversial. Hemodynamic changes related to SGLT2 inhibitors via natriuresis and osmotic diuresis are one potential mechanism. The Canadian Diabetes Association and European Society of Cardiology recently suggested SGLT2 inhibitors as an optimal anti-diabetic medication for patients with type 2 diabetes with overt CV disease. Further studies elucidating the potential mechanisms of cardio- and renoprotective effects of SGLT2 are needed.

Keywords: Cardiovascular safety, Empagliflozin, SGLT2 inhibitors

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Table 1.

Results of the EMPA-REG OUTCOME trial

	Empagliflozin (n = 4,687)	Placebo (n = 2,333)	HR (95% CI)	Non-inferiority	Superiority
Primary endpoint	490 (10.5)	282 (12.1)	0.86 (0.74∼0.99)	P < 0.001	P = 0.04
Key secondary endpoint	599 (12.8)	333 (14.3)	0.89 (0.78∼1.01)	P < 0.001	P = 0.08
Cardiovascular death	172 (3.7)	137 (5.9)	0.62 (0.49∼0.77)	NA	P < 0.001
Non-fatal myocardial infarction	213 (4.5)	121 (5.2)	0.87 (0.70∼1.09)	NA	P = 0.22
Non-fatal stroke	150 (3.2)	60 (2.6)	1.24 (0.92∼1.67)	NA	P = 0.16
Heart failure	126 (2.7)	95 (4.1)	0.65 (0.50∼0.85)	NA	P = 0.002
All-cause death	269 (5.7)	194 (8.3)	0.68 (0.57∼0.82)	NA	P = 0.001

Primary endpoint: composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke; pre-specified key secondary endpoints: time to first event (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina). EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; HR, hazard ratio; 95% CI, 95% confidence interval; NA, not applicable. Adapted from the article of Perseghin and Solini (Cardiovasc Diabetol 2016;15:85) [11].

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