Among patients with diabetes prescribed sodium glucose co-transporter 2 inhibitors (SGLT2i), those with co-existing stage 3 or higher chronic kidney disease (CKD) have an increased risk for hyperkalemia compared with those with stage 1, 2, or no CKD, according to a real-world study presented at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference.

Within 6 months of SGLT2i initiation, 2.5% of 1630 patients with diabetes newly had serum potassium concentrations of 5.6 to 6 mEq/L and 1.3% exceeded 6 mEq/L, Harish Shanthanu Seethapathy, MBBS, and colleagues from Massachusetts General Hospital in Boston, Massachusetts, reported. Incidence rates were 3.2% and 1.3% among canagliflozin users, 2.1% and 1.4% among empagliflozin users, and 3.2% and 0% among dapagliflozin users, respectively.

Hyperkalemia developed in twice as many SGLT2i users with an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 compared with those who had an eGFR at or above that level: 21% vs 10% (P <.01). Patients with an eGFR of less than 30 mL/min/1.73 m2 were particularly prone to moderate to severe hyperkalemia. Overall, patients who also received an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor (ARB) blocker at baseline had higher risks for serum potassium of 5.6 to 6 mEq/L (2.8% vs 1.5%) and more than 6 mEq/L (1.4% vs 1.2%) compared with patients not receiving these renin angiotensin system inhibitors, respectively.

In addition, hyponatremia (serum sodium level less than 135 mEq/L) developed in 11.8% of SGLT2i users, hypermagnesemia (more than 2.4 mEq/L) in 0.5%, and hyperphosphatemia (serum phosphorus more than 4.5 mEq/L) in 0.2%. Incidence rates of these electrolyte abnormalities varied by SGLT2i drug.

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According to Dr Seethapathy’s team, the osmotic diuresis and natriuresis induced by SGLT2i produce changes in serum levels of electrolytes such as potassium and sodium. “Effective monitoring and treatment strategies are needed to mitigate such risks,” they wrote.

Of the cohort, 63% were male, 71% White, 12% had an HbA1C exceeding 10 g/dL at baseline, 18% had an eGFR of less than 60 mL/min/1.73 m2, and 79% were taking an ACE inhibitor or ARB. At baseline, 5% of patients had elevated potassium of more than 5 mEq/L and were excluded from some analyses.

Disclosure: This clinical trial was supported by Relypsa. Please see the original reference for a full list of authors’ disclosures.


Shanthanu Seethapathy H, Zhao S, Allegretti AS, Kalim S, Nigwekar SU. Large database longitudinal assessment of electrolyte abnormalities in diabetic patients receiving SGLT2 inhibitors. Presented at: Kidney Week 2020 Reimagined, October 19-25, 2020. Poster PO0967.