Considerations for best practices related to sodium-glucose cotransporter-2 inhibitors and serum potassium levels

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Pamulapati and colleagues developed guidance on best practices for safe use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors through an expert panel Delphi consensus process.¹ Their study identified 36 best practice statements related to SGLT-2 inhibitor use, and we commend the authors on creating a prescribing checklist for clinicians to consider, to facilitate the prescribing and monitoring of these agents. We do want to bring attention to the best practice statements related to serum potassium levels. The authors include a best practice statement to use caution when prescribing SGLT-2 inhibitors in persons at high risk for hyperkalemia, including those taking medications that may elevate serum potassium, such as an angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and/or a mineralocorticoid receptor antagonist (MRA). This statement originated from an initial hypothesis that the combination of increased glucagon and decreased insulin levels caused by SGLT-2 inhibitors increases serum potassium levels through its redistribution from intracellular to extracellular fluid.² Given the recommendation to use these agents in combination with an ACEI, ARB, or ARNI and/or MRA in patients with heart failure reduced ejection fraction (HFrEF), and their nephroprotective effect in patients with chronic kidney disease (CKD) irrespective of diabetes status, the risk of hyperkalemia with these agents has been further evaluated.^3-7 Literature assessing the risk of hyperkalemia with SGLT-2 inhibitor use suggests that changes to serum potassium levels are not a concern specific to these agents and therefore should not be factored into considerations for their initiation.