Effect of canagliflozin on white blood cell counts in patients with type 2 diabetes and heart failure: A subanalysis of the randomized CANDLE trial

Aims/Introduction Clinical evidence is lacking about the influence of sodium-glucose cotransporter 2 inhibitors on white blood cell (WBC) counts, a commonly used and widely available marker of inflammation. The aim of the present analysis was to assess the effect of canagliflozin relative to glimepiride on WBC counts. Materials and Methods This was a post-hoc subanalysis of the CANDLE trial (Effects of Canagliflozin in Patients with Type 2 Diabetes and Chronic Heart Failure: A Randomized Trial; UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. A total of 233 patients with type 2 diabetes and concomitant heart failure were randomly assigned to either canagliflozin (n = 113) or glimepiride (n = 120) treatment for 24 weeks. Overall, patient baseline characteristics were as follows: mean +/- standard deviation age, 68.6 +/- 10.1 years; hemoglobin A1c, 7.0 +/- 0.9%; left ventricular ejection fraction, 56.7 +/- 14.4%; and median N-terminal pro-brain natriuretic peptide, 252 pg/mL (interquartile range 96-563 pg/mL). The mean baseline WBC counts were 6704 cells/mu L (95% confidence interval 6,362-7,047) in the canagliflozin group and 6322 cells/mu L (95% confidence interval 5,991-6,654) in the glimepiride group. There were no significant differences between treatment groups in terms of changes in WBC counts from baseline to weeks 4 and 12. In contrast, a group difference (canagliflozin minus glimepiride) from baseline to week 24 was significant (mean difference - 456 cells/mu L [95% confidence interval -774 to -139, P = 0.005]). Conclusions Our findings suggest that 24 weeks of treatment with canagliflozin, relative to glimepiride, reduced WBC counts in patients with type 2 diabetes and heart failure.