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06-01-2015 | Type 2 diabetes | Article

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

Journal:
Diabetologia

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

Publisher: Springer Berlin Heidelberg

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

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