title: Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes.
abstract: OBJECTIVE
  Sodium-glucose co-transporter 2 (SGLT2) reabsorbs glucose and sodium in the renal proximal tubule. Dapagliflozin, an SGLT2 inhibitor, targets hyperglycaemia in type 2 diabetes by increasing renal glucose excretion. To investigate whether the parallel occurring sodium loss would have diuretic-like physiologic effects, we compared dapagliflozin and hydrochlorothiazide (HCTZ) effects on 24-h blood pressure (BP), body weight, plasma volume and glomerular filtration rate (GFR).
  
  
  METHODS
  In this randomized, placebo-controlled, double-blind trial, 75 subjects with type 2 diabetes were assigned placebo, dapagliflozin 10 mg/day, or HCTZ 25 mg/day. Changes from baseline BP, body weight, plasma volume and GFR were assessed after 12 weeks of treatment.
  
  
  RESULTS
  Subjects' mean age was 56 years, type 2 diabetes mellitus (T2DM) duration 6.3 years, and haemoglobin A1c (HbA1c) 7.5%. Treatment with placebo, dapagliflozin or HCTZ resulted in changes from baseline in 24-h ambulatory mean systolic blood pressure (SBP) of -0.9 (95%CI -4.2, +2.4), -3.3 (95%CI -6.8, +0.2), and -6.6 (95%CI -9.9, -3.2) mmHg, respectively at week 12, adjusted for baseline SBP. Body weight decreased with dapagliflozin and HCTZ. In a sub-study plasma volume appeared to decrease with dapagliflozin but did not change with placebo or HCTZ treatment. Dapagliflozin induced a greater reduction in GFR (-10.8%; 95%CI -14.6, -6.7) relative to placebo (-2.9%; 95% CI -6.9, +1.2) or HCTZ (-3.4%; 95%CI -7.3, +0.6).
  
  
  CONCLUSIONS
  Dapagliflozin-induced SGLT2 inhibition for 12 weeks is associated with reductions in 24-h BP, body weight, GFR and possibly plasma volume. Cumulatively, these effects suggest that dapagliflozin may have a diuretic-like capacity to lower BP in addition to beneficial effects on glycaemic control.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.j.lambers.heerspink@umcg.nl
authors.forename: H J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.forename: D
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: L
authors.initials: L
authors.lastname: Wie
authors.forename: B
authors.initials: B
authors.lastname: Leslie
authors.forename: J
authors.initials: J
authors.lastname: List
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005960:Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D004232:Diuretics; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D006852:Hydrochlorothiazide; C529054:dapagliflozin
keywords: HbA1c; blood pressure; dapagliflozin; renal function; type 2 diabetes