Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus

Aim: To evaluate the effects of canaglflozin on plasma volume, urinary glucose excretion (UGE), fasting plasma glucose (FRG), glycated haemoglobin (HbA1c) and additional measures of fluid/electrolyte balance in patients with type 2 diabetes on background therapy with metformin and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Methods: Patients (N= 36) were randomized (1 : 1) to receive canagliflozin 300 mg or placebo for 12 weeks. Pharmacodynamic parameters were assessed at baseline and at weeks 1 and 12. Results: Increased 24-h UGE was seen in the canagliflozin group compared with a reduction in the placebo group at both week 1)91.8 vs. -2.4 gl and week 12 (82.6 vs. -0.4 gl. Canagliflozin also reduced both ERG and HbAlc. Reductions in body weight and blood pressure were observed at weeks 1 and 12. Canagliflozin decreased plasma volume compared with an increase with placebo at week 1 (-5.4 vs. 4.30,6); p = 0.02), but this was largely attenuated at week 12 (4.6 vs. 5.8%; p = 0.76). A modest numerical increase in urine volume was observed with canagliflozin at week 1 that was attenuated at week 12; other measures of volume status (i.e. blood urea nitrogen, serum creatinine and haematocrit) remained modestly increased with canagliflozin at week 12. Conclusion: Canaglifloz n provided sustained effects on UGE and FRG over 12 weeks and a transient reduction in plasma volume that was largely attenuated by week 12.