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Published in: Diabetologia 6/2015

01-06-2015 | Short Communication

Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes

Authors: William T. Cefalu, Kaj Stenlöf, Lawrence A. Leiter, John P. H. Wilding, Lawrence Blonde, David Polidori, John Xie, Daniel Sullivan, Keith Usiskin, William Canovatchel, Gary Meininger

Published in: Diabetologia | Issue 6/2015

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Abstract

Aims/hypothesis

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/interpretation

In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA1c and SBP.
Trial registration: ClinicalTrials.gov NCT01081834; NCT01106625; NCT01106677; and NCT01106690
Appendix
Available only for authorised users
Literature
1.
go back to reference Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35:1364–1379CrossRefPubMedCentralPubMed Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35:1364–1379CrossRefPubMedCentralPubMed
3.
go back to reference Jensen MD, Ryan DH, Apovian CM et al (2014) 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129:S102–S138 Jensen MD, Ryan DH, Apovian CM et al (2014) 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129:S102–S138
5.
go back to reference Wing RR, Lang W, Wadden TA et al (2011) Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 34:1481–1486CrossRefPubMedCentralPubMed Wing RR, Lang W, Wadden TA et al (2011) Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 34:1481–1486CrossRefPubMedCentralPubMed
6.
go back to reference The Diabetes Prevention Program Research Group (2012) Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 35:731–737CrossRefPubMedCentral The Diabetes Prevention Program Research Group (2012) Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 35:731–737CrossRefPubMedCentral
7.
go back to reference Pi-Sunyer X, Blackburn G, Brancati FL et al (2007) Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 30:1374–1383CrossRefPubMed Pi-Sunyer X, Blackburn G, Brancati FL et al (2007) Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 30:1374–1383CrossRefPubMed
8.
go back to reference Wing RR, Bolin P, Brancati FL et al (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145–154CrossRefPubMed Wing RR, Bolin P, Brancati FL et al (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369:145–154CrossRefPubMed
9.
go back to reference Stenlöf K, Cefalu WT, Kim K-A et al (2013) Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 15:372–382CrossRefPubMedCentralPubMed Stenlöf K, Cefalu WT, Kim K-A et al (2013) Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 15:372–382CrossRefPubMedCentralPubMed
10.
go back to reference Lavalle-González FJ, Januszewicz A, Davidson J et al (2013) Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 56:2582–2592CrossRefPubMedCentralPubMed Lavalle-González FJ, Januszewicz A, Davidson J et al (2013) Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 56:2582–2592CrossRefPubMedCentralPubMed
11.
go back to reference Wilding JP, Charpentier G, Hollander P et al (2013) Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 67:1267–1282CrossRefPubMedCentralPubMed Wilding JP, Charpentier G, Hollander P et al (2013) Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract 67:1267–1282CrossRefPubMedCentralPubMed
12.
go back to reference Forst T, Guthrie R, Goldenberg R et al (2014) Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 16:467–477CrossRefPubMedCentralPubMed Forst T, Guthrie R, Goldenberg R et al (2014) Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab 16:467–477CrossRefPubMedCentralPubMed
13.
go back to reference Monami M, Dicembrini I, Marchionni N, Rotella CM, Mannucci E (2012) Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis. Exp Diabetes Res 2012:672658PubMedCentralPubMed Monami M, Dicembrini I, Marchionni N, Rotella CM, Mannucci E (2012) Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis. Exp Diabetes Res 2012:672658PubMedCentralPubMed
14.
go back to reference de las Cruces Souto-Gallardo M, Bacardi Gascon M, Jimenez Cruz A (2011) Effect of weight loss on metabolic control in people with type 2 diabetes mellitus: systematic review. Nutr Hosp 26:1242–1249 de las Cruces Souto-Gallardo M, Bacardi Gascon M, Jimenez Cruz A (2011) Effect of weight loss on metabolic control in people with type 2 diabetes mellitus: systematic review. Nutr Hosp 26:1242–1249
Metadata
Title
Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes
Authors
William T. Cefalu
Kaj Stenlöf
Lawrence A. Leiter
John P. H. Wilding
Lawrence Blonde
David Polidori
John Xie
Daniel Sullivan
Keith Usiskin
William Canovatchel
Gary Meininger
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 6/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3547-2

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