A meta-analysis gathered data from six trials assessing four sodium-glucose cotransporter 2 (SGLT2) inhibitors to look at risk for hyperkalemia among patients with type 2 diabetes and high cardiovascular (CV) risk or chronic kidney disease (CKD). It showed that SGLT2 inhibitors were associated with a significant reduction in hyperkalemia, across studies and a variety of subgroups, along with no increase in hypokalemia.
The study was published by Circulation on April 8. The following commentary by Kharisa Rachmasari, MD, and Victor M. Montori, MD, MSc, FACP, was published in the ACP Journal Club section of Annals of Internal Medicine on Sept. 6.
Hyperkalemia is a major limiting factor for the optimal use of agents that interfere with the renin-angiotensin-aldosterone system (RAAS) and improve outcomes in patients with diabetes and renal or cardiac impairment.
Neuen and colleagues' meta-analysis of individual-patient data from randomized trials found that SGLT2 inhibitors reduced risk for serious hyperkalemia (serum potassium level ≥6.0 mmol/L), with no increased risk for hypokalemia. Estimates of benefits were consistent with both large and trivial reductions in the risk for serious hyperkalemia.
The fact that SGLT2 inhibitors improve renal and CV outcomes may enable clinicians to initiate or intensify treatment with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or aldosterone-receptor blockers in patients with CKD or cardiac insufficiency. The combination of an SGLT2 inhibitor with one of these agents may improve renal and CV outcomes while reducing the risk for hyperkalemia.
SGLT2 inhibitors are costly in the USA, and their use is associated with increased risk for genitourinary infections and, rarely, euglycemic diabetes ketoacidosis. A reduced risk for severe hyperkalemia may justify their use not only as glucose-lowering agents for treatment of type 2 diabetes but also for improving CV and renal outcomes (alone and as adjuncts to RAAS inhibitors or blockers) in patients at high risk for severe hyperkalemia, with and without type 2 diabetes.