title: SGLT-2 Inhibitors and Cardiovascular Risk in Diabetes Mellitus: A Comprehensive and Critical Review of the Literature.
abstract: Diabetes mellitus is a major cardiovascular risk factor. Despite the vast pharmaceutical armamentarium, current therapeutic options for the treatment of type 2 diabetes mellitus were unable to provide consistent cardiovascular benefits, apart for metformin. The newest antidiabetic class of drugs, the SGLT-2 inhibitors, seem to provide significant survival benefits. The aim of this review is to present available data that will clarify whether SGLT-2 inhibitors could precipitate in reducing cardiovascular risk in diabetes mellitus.
  
  
  
  A comprehensive literature search was performed to identify available data from clinical and experimental studies evaluating the impact of SGLT-2 inhibitors in cardiovascular risk factors and outcomes.
  
  
  
  Along with a mild antihyperglycemic effect, SGLT-2 inhibitors seem to possess multi-dimensional properties, affecting positively several recognized cardiovascular risk factors such as increased blood pressure, arterial stiffness, body weight and dyslipidemia. Furthermore, preliminary data point towards additional benefits, including reduction of albuminuria in diabetic nephropathy, and reduction of oxidative markers and fatty liver disease in experimental models. The efficacy and safety profile of empagliflozin, an SGLT-2 inhibitor, was evaluated in the EMPA-REG outcome study, and the results were quite impressive. Further credence comes from the analysis of pooled data of SGLT-2 inhibitors trials that have shown similar results.
  
  
  
  SGLT-2 Inhibitors seem to be related with ameliorating effects on multiple cardiovascular risk factors. The first data from the EMPA-REG outcome study are indeed very promising. Several ongoing cardiovascular studies with this novel class of drugs will shed light and enforce or question current enthusiasm.
authors.affiliation: Second Propaedeutic Department of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Imprialos
authors.affiliation: VAMC and George Washington University, Washington, DC, Greece.
authors.forename: Charles
authors.initials: C
authors.lastname: Faselis
authors.affiliation: Second Propaedeutic Department of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Boutari
authors.affiliation: Second Propaedeutic Department of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stavropoulos
authors.affiliation: Second Propaedeutic Department of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Athyros
authors.affiliation: Second Propaedeutic Department of Medicine, Aristotle University, Thessaloniki, Greece.
authors.forename: Asterios
authors.initials: A
authors.lastname: Karagiannis
authors.affiliation: 49, Konstantinoupoleos Street, 54643 Thessaloniki, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Doumas
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
keywords: SGLT-2 inhibitors; albuminuria; blood pressure; body weight; cardiovascular events; cardiovascular risk; kidneys function; lipids