title: Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes.
abstract: OBJECTIVE
  Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA1c, body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA1c and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA1c and SBP reductions in patients with type 2 diabetes.
  
  
  METHODS
  Pooled data from four placebo-controlled Phase 3 studies (N = 2,250) in patients with type 2 diabetes were used in the analyses. In each study, patients were treated with placebo, canagliflozin 100 mg or canagliflozin 300 mg, once daily for 26 weeks. Changes from baseline in body weight, HbA1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA1c and SBP was obtained using ANCOVA.
  
  
  RESULTS
  Canagliflozin 100 and 300 mg reduced mean body weight, HbA1c and SBP compared with placebo (p < 0.001 for each), and more patients had body-weight reductions >0%, ≥5% and ≥10% with canagliflozin treatment than with placebo. Weight-loss-independent and weight-loss-associated mechanisms contributed to HbA1c and SBP lowering with canagliflozin: ~85% of HbA1c lowering and ~60% of SBP lowering was independent of weight loss.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA1c and SBP.
authors: Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA, 70808-4124, USA, william.cefalu@pbrc.edu.
authors: William T
authors: WT
authors: Cefalu
authors: Kaj
authors: K
authors: Stenlöf
authors: Lawrence A
authors: LA
authors: Leiter
authors: John P H
authors: JP
authors: Wilding
authors: Lawrence
authors: L
authors: Blonde
authors: David
authors: D
authors: Polidori
authors: John
authors: J
authors: Xie
authors: Daniel
authors: D
authors: Sullivan
authors: Keith
authors: K
authors: Usiskin
authors: William
authors: W
authors: Canovatchel
authors: Gary
authors: G
authors: Meininger
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D000068896:Canagliflozin / Q000008:administration & dosage* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013599:Systole / Q000187:drug effects; D015431:Weight Loss
chemical_list: D000068896:Canagliflozin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human