SGLT2 Inhibitors Reduce Hyperkalemia in High-Risk T2DM Patients

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.