TY  - JOUR
TI  - Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.
AV  - public
Y1  - 2021/12/21/
EP  - 4901
N2  - 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 ?6.0 and <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.
ID  - discovery10140960
KW  - Canagliflozin
KW  -  Chronic kidney disease
KW  -  Hyperkalaemia
KW  -  Potassium
KW  -  SGLT2 inhibitors
KW  -  Type 2 diabetes mellitus
VL  - 42
SP  - 4891
IS  - 48
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
UR  - https://doi.org/10.1093/eurheartj/ehab497
SN  - 1522-9645
JF  - European Heart Journal
A1  - Neuen, BL
A1  - Oshima, M
A1  - Perkovic, V
A1  - Agarwal, R
A1  - Arnott, C
A1  - Bakris, G
A1  - Cannon, CP
A1  - Charytan, DM
A1  - Edwards, R
A1  - Górriz, JL
A1  - Jardine, MJ
A1  - Levin, A
A1  - Neal, B
A1  - De Nicola, L
A1  - Pollock, C
A1  - Rosenthal, N
A1  - Wheeler, DC
A1  - Mahaffey, KW
A1  - Heerspink, HJL
ER  -