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

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 NCT01106690.

Fig. 1

Mean (SE) reduction in (a) HbA_1c, (b) body weight and (c) SBP. White bars, placebo; grey bars, canagliflozin 100 mg; black bars, canagliflozin 300 mg. (d–f) The cumulative distribution of change from baseline values for each measure. In each of these figures, the y coordinate represents the percentage of patients whose change from baseline value is lower than the change from baseline value represented by the x coordinate. Light grey dashed line, placebo; medium grey dashed–dotted line, canagliflozin 100 mg; solid black line, canagliflozin 300 mg. To convert values for change in HbA_1c in % into mmol/mol, multiply by 10.929. BW, body weight

Fig. 2

Relationship between changes in body weight and (a) HbA_1c and (b) SBP at week 26. Larger open symbols represent the mean change for the entire treatment group, and smaller symbols represent mean changes within each decile of weight change; white triangles, placebo; grey squares, canagliflozin 100 mg; black circles, canagliflozin 300 mg. To convert values for change in HbA_1c in % into mmol/mol, multiply by 10.929. BW, body weight