title: SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study.
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.
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX Diabetes and Obesity Clinical Research Center, Department of Medicine, Hamad General Hospital, Doha, Qatar abdulghani@uthscsa.edu.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Abdul-Ghani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
authors.affiliation: Division of Cardiology, University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, San Antonio, TX.
authors.forename: Robert
authors.initials: R
authors.lastname: Chilton
authors.affiliation: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX albarado@uthscsa.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D004573:Electrolytes / Q000097:blood; D023381:Endpoint Determination; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000077205:Pioglitazone; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004573:Electrolytes; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D045162:Thiazolidinediones; C089180:SLC5A2 protein, human; C570240:empagliflozin