title: Sodium-glucose Cotransporter 2 Inhibitors (SGLT2i): Their Role in Cardiometabolic Risk Management.
abstract: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin.
  
  
  
  The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function.
  
  
  
  SGLT2i improve several CV risk factors, including fasting and postprandial plasma glucose levels, lipids, blood pressure, body weight, serum uric acid and arterial stiffness. These drugs may also favorably modulate cardiac and renal function via their effects on inflammation, oxidative stress, diuresis, fluid and sodium retention, myocardial function, vascular resistance and 'fuel' metabolism. In the EMPA-REG OUTCOME study, the first published large CV outcome SGLT2i trial, empagliflozin significantly reduced the primary composite outcome (i.e. CV death, nonfatal myocardial infarction or stroke) and all-cause death as well as hospitalization for heart failure. In addition, empagliflozin was associated with a slower progression of kidney disease and lower rates of clinically relevant renal events than was placebo when added to standard care in patients at high CV risk.
  
  
  
  Multiple metabolic benefits may account for the positive clinical outcomes in the EMPA-REG OUTCOME study. Ongoing CV outcome trials involving other SGLT2i will help establish whether the reported CV and microvascular risk benefits are compound-specific or drug class effects.
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle; University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Katsiki
authors.affiliation: Dept. of Clinical Biochemistry, Royal Free Hospital campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, United Kingdom.
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.affiliation: Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Theodorakis
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D012307:Risk Factors; D012308:Risk Management; 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: Dapagliflozin; canagliflozin; cardiovascular
  outcome trials; cardiovascular risk factors; empagliflozin; microvascular complications; renoprotection; sodium-glucose cotransporter 2 inhibitors