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Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.

Neuen, BL; Oshima, M; Perkovic, V; Agarwal, R; Arnott, C; Bakris, G; Cannon, CP; ... Heerspink, HJL; + view all (2021) Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. European Heart Journal , 42 (48) pp. 4891-4901. 10.1093/eurheartj/ehab497.

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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 ≥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.

Type: Article
Title: Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.
Location: England
DOI: 10.1093/eurheartj/ehab497
Publisher version: https://doi.org/10.1093/eurheartj/ehab497
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Canagliflozin, Chronic kidney disease, Hyperkalaemia, Potassium, SGLT2 inhibitors, Type 2 diabetes mellitus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10140960
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