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/μL (95% confidence interval 6,362–7,047) in the canagliflozin group and 6322 cells/μL (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/μL [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.