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Effects of canagliflozin on body weight and relationship to HbA 1c and blood pressure changes in patients with type 2 diabetes

Byline: William T. Cefalu (1), Kaj Stenlof (2), Lawrence A. Leiter (3), John P. H. Wilding (4), Lawrence Blonde (5), David Polidori (6), John Xie (7), Daniel Sullivan (7), Keith Usiskin (7), William Canovatchel (7), Gary Meininger (7) Keywords: Body weight; Canagliflozin; Sodium glucose co-transport... Full description

Journal Title: Diabetologia 2015, Vol.58(6), pp.1183-1187
Main Author: Cefalu, William
Other Authors: Stenlöf, Kaj , Leiter, Lawrence , Wilding, John , Blonde, Lawrence , Polidori, David , Xie, John , Sullivan, Daniel , Usiskin, Keith , Canovatchel, William , Meininger, Gary
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0012-186X ; E-ISSN: 1432-0428 ; DOI: 10.1007/s00125-015-3547-2
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recordid: springer_jour10.1007/s00125-015-3547-2
title: Effects of canagliflozin on body weight and relationship to HbA 1c and blood pressure changes in patients with type 2 diabetes
format: Article
creator:
  • Cefalu, William
  • Stenlöf, Kaj
  • Leiter, Lawrence
  • Wilding, John
  • Blonde, Lawrence
  • Polidori, David
  • Xie, John
  • Sullivan, Daniel
  • Usiskin, Keith
  • Canovatchel, William
  • Meininger, Gary
subjects:
  • Body weight
  • Canagliflozin
  • Sodium glucose co-transporter 2 (SGLT2) inhibitor
  • Type 2 diabetes mellitus
ispartof: Diabetologia, 2015, Vol.58(6), pp.1183-1187
description: Byline: William T. Cefalu (1), Kaj Stenlof (2), Lawrence A. Leiter (3), John P. H. Wilding (4), Lawrence Blonde (5), David Polidori (6), John Xie (7), Daniel Sullivan (7), Keith Usiskin (7), William Canovatchel (7), Gary Meininger (7) Keywords: Body weight; Canagliflozin; Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus Abstract: Aims/hypothesis Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA.sub.1c, body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA.sub.1c and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA.sub.1c 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, HbA.sub.1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA.sub.1c and SBP was obtained using ANCOVA. Results Canagliflozin 100 and 300 mg reduced mean body weight, HbA.sub.1c and SBP compared with placebo (p0%, a[yen]5% and a[yen]10% with canagliflozin treatment than with placebo. Weight-loss-independent and weight-loss-associated mechanisms contributed to HbA.sub.1c and SBP lowering with canagliflozin: ~85% of HbA.sub.1c lowering and ~60% of SBP lowering was independent of weight loss. Conclusions/interpretation In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA.sub.1c and SBP. Trial registration: ClinicalTrials.gov NCT01081834 NCT01106625 NCT01106677 and NCT01106690 Author Affiliation: (1) Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA, 70808-4124, USA (2) Clinical Trial Center, Sahlgrenska University Hospital, Gothenburg, Sweden (3) Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St Michael's Hospital, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada (4) Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK (5) Department of Endocrinology, Diabetes, and
language: eng
source:
identifier: ISSN: 0012-186X ; E-ISSN: 1432-0428 ; DOI: 10.1007/s00125-015-3547-2
fulltext: fulltext_linktorsrc
issn:
  • 1432-0428
  • 14320428
  • 0012-186X
  • 0012186X
url: Link


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titleEffects of canagliflozin on body weight and relationship to HbA 1c and blood pressure changes in patients with type 2 diabetes
creatorCefalu, William ; Stenlöf, Kaj ; Leiter, Lawrence ; Wilding, John ; Blonde, Lawrence ; Polidori, David ; Xie, John ; Sullivan, Daniel ; Usiskin, Keith ; Canovatchel, William ; Meininger, Gary
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descriptionByline: William T. Cefalu (1), Kaj Stenlof (2), Lawrence A. Leiter (3), John P. H. Wilding (4), Lawrence Blonde (5), David Polidori (6), John Xie (7), Daniel Sullivan (7), Keith Usiskin (7), William Canovatchel (7), Gary Meininger (7) Keywords: Body weight; Canagliflozin; Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus Abstract: Aims/hypothesis Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA.sub.1c, body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA.sub.1c and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA.sub.1c 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, HbA.sub.1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA.sub.1c and SBP was obtained using ANCOVA. Results Canagliflozin 100 and 300 mg reduced mean body weight, HbA.sub.1c and SBP compared with placebo (p<0.001 for each), and more patients had body-weight reductions >0%, a[yen]5% and a[yen]10% with canagliflozin treatment than with placebo. Weight-loss-independent and weight-loss-associated mechanisms contributed to HbA.sub.1c and SBP lowering with canagliflozin: ~85% of HbA.sub.1c lowering and ~60% of SBP lowering was independent of weight loss. Conclusions/interpretation In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA.sub.1c and SBP. Trial registration: ClinicalTrials.gov NCT01081834 NCT01106625 NCT01106677 and NCT01106690 Author Affiliation: (1) Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA, 70808-4124, USA (2) Clinical Trial Center, Sahlgrenska University Hospital, Gothenburg, Sweden (3) Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St Michael's Hospital, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada (4) Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK (5) Department of Endocrinology, Diabetes, and Metabolic Diseases, Ochsner Medical Center, New Orleans, LA, USA (6) Janssen Research & Development, LLC, San Diego, CA, USA (7) Janssen Research & Development, LLC, Raritan, NJ, USA Article History: Registration Date: 24/02/2015 Received Date: 21/10/2014 Accepted Date: 12/02/2015 Online Date: 27/03/2015 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00125-015-3547-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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