SGLT2 inhibitors and cardiovascular risk

Lessons learned from the EMPA-REG Outcome study

Muhammad A Abdul-ghani, Stefano Del Prato, Robert J Chilton, Ralph A Defronzo

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%. This beneficial effect was driven by a 38% reduction in CV mortality with no significant decrease in nonfatal myocardial infarction or stroke. Empagliflozin also caused a 35% reduction in hospitalization for heart failure without affecting hospitalization for unstable angina. Although sodium-glucose cotransporter 2 inhibitors exert multiple metabolic benefits (decreases in HbA1c, body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, it is unlikely that the reduction in CV mortality can be explained by empagliflozin's metabolic effects. More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization. In this Perspective, we will discuss possible mechanisms for these beneficial effects of empagliflozin and their implications for the care of T2DM patients.

Original languageEnglish (US)
Pages (from-to)717-725
Number of pages9
JournalDiabetes Care
Volume39
Issue number5
DOIs
StatePublished - May 1 2016

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Outcome Assessment (Health Care)
Hospitalization
Mortality
Type 2 Diabetes Mellitus
Heart Failure
Sodium-Glucose Transport Proteins
Stroke
Myocardial Infarction
Blood Pressure
Unstable Angina
HDL Cholesterol
empagliflozin
Cause of Death
Patient Care
Cardiovascular Diseases
Hemodynamics
Body Weight
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

SGLT2 inhibitors and cardiovascular risk : Lessons learned from the EMPA-REG Outcome study. / Abdul-ghani, Muhammad A; Del Prato, Stefano; Chilton, Robert J; Defronzo, Ralph A.

In: Diabetes Care, Vol. 39, No. 5, 01.05.2016, p. 717-725.

Research output: Contribution to journalArticle

Abdul-ghani, Muhammad A ; Del Prato, Stefano ; Chilton, Robert J ; Defronzo, Ralph A. / SGLT2 inhibitors and cardiovascular risk : Lessons learned from the EMPA-REG Outcome study. In: Diabetes Care. 2016 ; Vol. 39, No. 5. pp. 717-725.
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