title: Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.
abstract: BACKGROUND
  Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.
  
  
  OBJECTIVE
  Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.
  
  
  METHODS
  This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.
  
  
  METHODS
  Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin.
  
  
  METHODS
  Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk.
  
  
  METHODS
  Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated.
  
  
  RESULTS
  At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, -2.08 kg [95% confidence interval (CI)=-2.84 to -1.31; P<0.0001]; waist circumference, -1.52 cm (95% CI=-2.74 to -0.31; P=0.0143); FM, -1.48 kg (95% CI=-2.22 to -0.74; P=0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI=15.5 to 36.7; P<0.0001); VAT, -258.4 cm3 (95% CI=-448.1 to -68.6; nominal P=0.0084); SAT, -184.9 cm3 (95% CI=-359.7 to -10.1; nominal P=0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%.
  
  
  CONCLUSIONS
  Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.
authors.affiliation: Department of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden. Jan.Bolinder@ki.se
authors.forename: Jan
authors.initials: J
authors.lastname: Bolinder
authors.forename: Östen
authors.initials: Ö
authors.lastname: Ljunggren
authors.forename: Joel
authors.initials: J
authors.lastname: Kullberg
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.forename: John
authors.initials: J
authors.lastname: Wilding
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Langkilde
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sugg
authors.forename: Shamik
authors.initials: S
authors.lastname: Parikh
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds; D001786:Blood Glucose; D050218:Body Fat Distribution; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; C529054:dapagliflozin; D008687:Metformin