Hyperkalemia can occur in people with type 2 diabetes, especially in those with chronic kidney disease (CKD), and is clinically important because it can lead to life-threatening arrhythmias.
A recent study suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of serious hyperkalemia (serum potassium ≥6.0 mmol/L) with no increased risk of hypokalemia in patients with CKD and/or cardiovascular risk. The study findings were published in the journal Circulation on April 08, 2022.

SGLT2 inhibitors reduce the risk of cardiorenal events in people with type 2 diabetes at high cardiovascular risk or with CKD. However, their effect on hyperkalemia has not been systematically evaluated. Therefore, Dr Brendon L. Neuen and his team conducted a study to evaluate the effect of SGLT2 inhibitors in people with type 2 diabetes at high cardiovascular risk and/or with CKD.
In this meta-analysis, the researchers used individual participant data from randomized, double-blind, placebo-controlled clinical outcome trials with SGLT2 inhibitors in people with type 2 diabetes at high cardiovascular risk and/or with CKD, in which serum potassium levels were routinely measured. The major outcome assessed was time to serious hyperkalemia, determined as central laboratory determine serum potassium ≥6.0 mmol/L, with other outcomes including investigator-reported hyperkalemia events and hypokalemia (serum potassium ≤3.5 mmol/L). They performed cox regression analyses were performed to estimate treatment effects from each trial with hazards ratios (HR) and corresponding 95% CI pooled using random-effects models to obtain summary treatment effects, overall and across key subgroups.
Key findings of the study:
The researchers evaluated data from six trials comprising 49,875 participants assessing four SGLT2 inhibitors.
Upon analysis, the researchers observed that 1,754 participants developed serious hyperkalemia and an additional 1,119 investigator-reported hyperkalemia events.
They found that the SGLT2 inhibitors reduced the risk of serious hyperkalemia (HR 0.84, 95% CI 0.76-0.93), an effect consistent across studies.
They noted that the incidence of investigator-reported hyperkalemia was also lower with SGLT2 inhibitors (HR 0.80).
They reported that the reductions in serious hyperkalemia were observed across a range of subgroups including baseline kidney function, history of heart failure, RAAS inhibitor, diuretic and MRA use.
They further noted that the SGLT2 inhibitors did not increase the risk of hypokalemia (HR 1.04, 95% CI 0.94-1.15).
The authors concluded, "SGLT2 inhibitors reduce the risk of serious hyperkalemia in people with type 2 diabetes at high cardiovascular risk and/or with CKD, without increasing the risk of hypokalemia."
For further information:
DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.057736
Keywords:
SGLT2 inhibitors, chronic kidney disease, hypokalemia, hyperkalemia, arrythmia, cardiovascular risk, cardiorenal events, sodium-glucose cotransporter 2 inihibitor, CV risk, CKD, journal Circulation.