TY  - JOUR
A1  - Zinman, Bernard
A1  - Inzucchi, Silvio E.
A1  - Lachin, John M.
A1  - Wanner, Christoph
A1  - Ferrari, Roberto
A1  - Fitchett, David
A1  - Bluhmki, Erich
A1  - Hantel, Stefan
A1  - Kempthorne-Rawson, Joan
A1  - Newman, Jennifer
A1  - Johansen, Odd Erik
A1  - Woerle, Hans-Juergen
A1  - Broedl, Uli C.
T1  - Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME (TM))
T2  - Cardiovascular Diabetology
N2  - Background: Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. The aim of the ongoing EMPA-REG OUTCOME (TM) trial is to determine the long-term CV safety of empagliflozin, as well as investigating potential benefits on macro-/microvascular outcomes. 
Methods: Patients who were drug naive (HbA(1c) >= 7.0% and <= 9.0%), or on background glucose-lowering therapy (HbA(1c) >= 7.0% and <= 10.0%), and were at high risk of CV events, were randomized (1:1:1) and treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo (double blind, double dummy) superimposed upon the standard of care. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. CV events will be prospectively adjudicated by an independent Clinical Events Committee. The trial will continue until >= 691 confirmed primary outcome events have occurred, providing a power of 90% to yield an upper limit of the adjusted 95% CI for a hazard ratio of <1.3 with a one-sided a of 0.025, assuming equal risks between placebo and empagliflozin (both doses pooled). Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes (time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina pectoris) where non-inferiority is achieved. 
Results: Between Sept 2010 and April 2013, 592 clinical sites randomized and treated 7034 patients (41% from Europe, 20% from North America, and 19% from Asia). At baseline, the mean age was 63 +/- 9 years, BMI 30.6 +/- 5.3 kg/m(2), HbA1c 8.1 +/- 0.8%, and eGFR 74 +/- 21 ml/min/1.73 m(2). The study is expected to report in 2015. 
Discussion: EMPA REG OUTCOME (TM) will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk, with the potential to show cardioprotection.
KW  - glycemic control
KW  - blood pressure
KW  - macrovascular
KW  - doule blind
KW  - chronic kidney disease
KW  - type-1 diabetes mellitus
KW  - safety
KW  - metformin
KW  - add-on
KW  - albuminuria
KW  - sulfonylurea
KW  - efficacy
KW  - canagliflozin
KW  - microvascular
KW  - SGLT2 inhibitor
KW  - type 2 diabetes
KW  - body weight
KW  - empagliflozin
Y1  - 2014
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/11603
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-116036
SN  - 1475-2840
VL  - 13
IS  - 102
ER  -