Effects of canagliflozin on serum potassium in the canvas program

Background: Canagliflozin (CANA) is a sodium glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of type 2 diabetes mellitus (T2DM). The US label Warnings and Precautions section notes a risk of hyperkalemia with CANA in patients with moderate renal impairment who are taking medications that interfere with potassium excretion. Serum potassium levels were assessed in patients at high cardiovascular (CV) risk in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, comprised of the CANVAS and CANVAS-R trials. Methods: The CANVAS Program randomized 10,142 participants with T2DM and high CV risk to CANA or placebo (PBO); 80% were on renin-angiotensin aldosterone system (RAAS) inhibitors at baseline. Serum potassium measurements were performed in a central laboratory; values meeting predefined limit of change criteria (PDLC) were prespecified and assessed using results obtained up to 2 days after the last dose of study drug. Results: In the CANVAS Program, the risk of decreased serum potassium (PDLC <3.4 mEq/L and >15% decrease from baseline) was similar between the CANA and PBO arms (Table; hazard ratio [HR] 0.96 [95% confidence interval (CI) 0.72, 1.28]). The HR (95% CI) for increased serum potassium (PDLC >5.4 mEq/L and >15% increase from baseline) was 1.03 (0.89, 1.20) and for serum potassium ≥6.5 mEq/L was 0.84 (0.50, 1.41). Generally similar results were seen in subgroups by baseline eGFR (<45, 45-<60, & ≥60 mL/min/1.73 m2; Table). Conclusions: In the CANVAS Program, no significant differences in the risk of hypoor hyperkalemia were observed with CANA versus PBO overall or in participants with renal impairment. (Table Presented).