Diabetology Xagena

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

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 chronic kidney disease, sodium‒glucose cotransporter 2 ( SGLT2 ) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.

The CREDENCE trial randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to the SGLT2 inhibitor Canagliflozin ( Invokana ) or matching placebo.

In a post hoc analysis using an intention-to-treat approach, researchers have assessed the effect of Canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders.
They also analysed effects on central laboratory-determined hyper- and hypokalaemia ( serum potassium greater than or equal to 6.0 and less than 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 has 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.

In conclusion, among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with Canagliflozin may reduce the risk of hyperkalaemia in people with type 2 diabetes mellitus and chronic kidney disease without increasing the risk of hypokalaemia. ( Xagena )

Neuen BL et al, Eur Heart J 2021; Online ahead of print