title: SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment.
abstract: BACKGROUND
  Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) offer a new opportunity for the management of type 2 diabetes mellitus. These agents reduce hyperglycemia by decreasing the renal glucose threshold and thereby increasing urinary glucose excretion. Subsequent reduction of glucotoxicity improves beta-cell sensitivity to glucose and tissue insulin sensitivity.
  
  
  METHODS
  This article analyzes the efficacy and safety data of canagliflozin, dapagliflozin and empagliflozin in randomized controlled trials of 24 - 104 weeks duration, compared with placebo or an active comparator, in patients treated with diet/exercise, metformin, dual oral therapy or insulin.
  
  
  CONCLUSIONS
  SGLT2 inhibitors significantly and consistently reduce glycated hemoglobin, with a minimal risk of hypoglycemia. The improvement of glucose control is similar or slightly better compared with metformin, sulfonylureas or sitagliptin, with the add-on value of significant reductions in body weight and blood pressure. However, caution is recommended in fragile elderly patients and patients with chronic kidney disease. An increased risk of genital mycotic infections is observed, but urinary tract infections are rare. Concern about an unexpected risk of euglycemic ketoacidosis has been recently reported. A possible renal protection deserves further attention. A remarkable reduction in cardiovascular mortality was reported in EMPA-REG OUTCOME with empagliflozin.
authors.affiliation: a Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM) , University of Liège , Liège , Belgium.|b Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine , CHU Liège , Liège B-4000 , Belgium.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D000068896:Canagliflozin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007333:Insulin Resistance; D016032:Randomized Controlled Trials as Topic; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C529054:dapagliflozin; C570240:empagliflozin; D005947:Glucose
keywords: SGLT2 inhibitor; canagliflozin; dapagliflozin; empagliflozin; oral antidiabetic drug; type 2 diabetes mellitus