@article{discovery10140960,
           pages = {4891--4901},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
          volume = {42},
         journal = {European Heart Journal},
           title = {Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.},
            year = {2021},
           month = {December},
          number = {48},
        keywords = {Canagliflozin, Chronic kidney disease, Hyperkalaemia, Potassium, SGLT2 inhibitors, Type 2 diabetes mellitus},
        abstract = {Aims: Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin-aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.
Methods and results: The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium {$\ge$}6.0 and {\ensuremath{<}}3.5 mmol/L, respectively) and change in serum potassium. At baseline, the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9\%) participants were receiving renin-angiotensin system blockade. The incidence of investigator-reported hyperkalaemia or initiation of potassium binders was lower with canagliflozin than with placebo [occurring in 32.7 vs. 41.9 participants per 1000 patient-years; hazard ratio (HR) 0.78, 95\% confidence interval (CI) 0.64-0.95, P = 0.014]. Canagliflozin similarly reduced the incidence of laboratory-determined hyperkalaemia (HR 0.77, 95\% CI 0.61-0.98, P = 0.031), with no effect on the risk of hypokalaemia (HR 0.92, 95\% CI 0.71-1.20, P = 0.53). The mean serum potassium over time with canagliflozin was similar to that of placebo. // Conclusion: Among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia.},
            issn = {1522-9645},
          author = {Neuen, BL and Oshima, M and Perkovic, V and Agarwal, R and Arnott, C and Bakris, G and Cannon, CP and Charytan, DM and Edwards, R and G{\'o}rriz, JL and Jardine, MJ and Levin, A and Neal, B and De Nicola, L and Pollock, C and Rosenthal, N and Wheeler, DC and Mahaffey, KW and Heerspink, HJL},
             url = {https://doi.org/10.1093/eurheartj/ehab497}
}