Cefalu, William T.; Stenlof, Kaj; Leiter, Lawrence A.; Wilding, John P. H.; Blonde, Lawrence; Polidori, David; Xie, John; Sullivan, Daniel; Usiskin, Keith; Canovatchel, William; Meininger, Gary
Abstract
Aims/hypothesis Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA(1c), body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA(1c) and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA(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(1c) and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA(1c) and SBP was obtained using ANCOVA.; Results Canagliflozin 100 and 300 mg reduced mean body weight, HbA(1c) 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 HbA(1c) and SBP lowering with canagliflozin: similar to 85% of HbA(1c) lowering and similar to 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(1c) and SBP.
