Physicians' Academy for Cardiovascular Education

SGLT2 inhibitor reduces total burden of CVD in patients with T2DM and ASCVD

Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial

Literature - McGuire DK, Zinman B, Inzucchi SE, et al. - Lancet Diabetes Endocrinol 2020; 8: 949–59,

Introduction and methods

In the EMPA-REG OUTCOME trial, treatment with empagliflozin reduced the risk of major adverse CV events (MACE), a composite of time to first event of CV death, non-fatal MI or non-fatal stroke, compared to placebo in patients with type 2 diabetes and established atherosclerotic CVD (RR 0.86, 95%CI: 0.74-0.99,P=0.038) [1]. In addition, secondary analyses showed that empagliflozin reduced risk of CV and all-cause mortality, hospitalization for heart failure and progression of diabetic kidney disease [2,3].

Analyses of total events (first plus recurrent events) are more frequently being used as they reflect the total morbidity burden. This prespecified analysis examined the effects of empagliflozin on total CV events in the EMPA-REG OUTCOME trial.

The EMPA-REG OUTCOME trial was a placebo-controlled randomized trial evaluating the effect of empagliflozin (10 mg and 25 mg) versus placebo in 7020 patients. Eligible patients were ≥18 years, had T2DM, HbA1c of 7-10%, prevalent CVD and eGFR ≥30 mL/min/1.73 m2. Primary outcome of the trial was MACE, a composite of death from CV causes, non-fatal MI or non-fatal stroke. Key secondary outcome was 4-point MACE, including also admission to hospital for unstable angina. Median follow-up was 3.2 (2.2-3.6) years in the pooled empagliflozin group and 3.1 (2.2-3.5) years in the placebo group.

Main results


In this secondary analysis of the EMPA-REG OUTCOME trial, empagliflozin reduced total outcome events (first plus recurrent events) compared to placebo in patients with T2DM and ASCVD. More specifically, risk of total events of MACE, 4-point MACE, coronary heart disease outcomes, HF outcomes and all-cause admission to hospital were reduced by empagliflozin compared to placebo.


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Find this article online at Lancet Diabetes Endocrinol

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