eprintid: 10140960
rev_number: 28
eprint_status: archive
userid: 608
dir: disk0/10/14/09/60
datestamp: 2022-01-07 17:34:02
lastmod: 2022-08-24 06:12:31
status_changed: 2022-01-07 17:34:02
type: article
metadata_visibility: show
creators_name: Neuen, BL
creators_name: Oshima, M
creators_name: Perkovic, V
creators_name: Agarwal, R
creators_name: Arnott, C
creators_name: Bakris, G
creators_name: Cannon, CP
creators_name: Charytan, DM
creators_name: Edwards, R
creators_name: Górriz, JL
creators_name: Jardine, MJ
creators_name: Levin, A
creators_name: Neal, B
creators_name: De Nicola, L
creators_name: Pollock, C
creators_name: Rosenthal, N
creators_name: Wheeler, DC
creators_name: Mahaffey, KW
creators_name: Heerspink, HJL
title: Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
keywords: Canagliflozin, Chronic kidney disease, Hyperkalaemia, Potassium, SGLT2 inhibitors, Type 2 diabetes mellitus
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
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.
date: 2021-12-21
date_type: published
official_url: https://doi.org/10.1093/eurheartj/ehab497
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1890591
doi: 10.1093/eurheartj/ehab497
pii: 6356221
lyricists_name: Wheeler, David
lyricists_id: DWHEE12
actors_name: Barczynska, Patrycja
actors_id: PBARC91
actors_role: owner
full_text_status: public
publication: European Heart Journal
volume: 42
number: 48
pagerange: 4891-4901
event_location: England
issn: 1522-9645
citation:        Neuen, BL;    Oshima, M;    Perkovic, V;    Agarwal, R;    Arnott, C;    Bakris, G;    Cannon, CP;                                                 ... Heerspink, HJL; + view all <#>        Neuen, BL;  Oshima, M;  Perkovic, V;  Agarwal, R;  Arnott, C;  Bakris, G;  Cannon, CP;  Charytan, DM;  Edwards, R;  Górriz, JL;  Jardine, MJ;  Levin, A;  Neal, B;  De Nicola, L;  Pollock, C;  Rosenthal, N;  Wheeler, DC;  Mahaffey, KW;  Heerspink, HJL;   - view fewer <#>    (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 <https://doi.org/10.1093/eurheartj%2Fehab497>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10140960/1/Wheeler_CREDENCE_hyperkalemia_EHJsubmission_final%20as%20resubmitted.pdf