What are the risks of hyperkalemia in a patient with type 2 diabetes taking Jardiance (empagliflozin) and how can it be managed, particularly in those with impaired renal function or taking other medications that increase potassium levels, such as Angiotensin-Converting Enzyme (ACE) inhibitors or potassium-sparing diuretics?

Jardiance and Hyperkalemia Risk

Jardiance (empagliflozin) actually reduces the risk of hyperkalemia by 16% in patients with type 2 diabetes, particularly those taking ACE inhibitors or other RAAS inhibitors, making it a protective agent rather than a risk factor for elevated potassium levels. 1

Protective Effect of SGLT2 Inhibitors on Hyperkalemia

• SGLT2 inhibitors like Jardiance reduce the risk of serious hyperkalemia (potassium ≥6.0 mmol/L) with a hazard ratio of 0.84 (95% CI 0.76-0.93), representing a 16% risk reduction compared to placebo. 1

• This protective effect is consistent across patients with varying degrees of renal impairment, those with heart failure, and importantly, those already taking RAAS inhibitors (ACE inhibitors, ARBs) or mineralocorticoid receptor antagonists. 1

• Jardiance does not increase the risk of hypokalemia (HR 1.04,95% CI 0.94-1.15), making it safe from a potassium balance perspective. 1

Strategic Use in High-Risk Patients

The American Journal of Kidney Diseases recommends initiating an SGLT2 inhibitor in patients with type 2 diabetes and impaired renal function experiencing hyperkalemia, if eGFR ≥20 mL/min/1.73 m², as this allows continuation of essential RAAS inhibitor therapy while reducing hyperkalemia risk. 2

• For patients on ACE inhibitors (like lisinopril) who develop hyperkalemia, adding Jardiance is preferred over discontinuing the ACE inhibitor, as this maintains cardiovascular and renal protection while lowering potassium levels. 2, 3

• The protective effect against hyperkalemia is observed even in patients taking multiple potassium-raising medications simultaneously, including ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists. 1

Renal Function Considerations

• Jardiance can be initiated if eGFR ≥20 mL/min/1.73 m² and should be continued even if eGFR subsequently falls below 20 mL/min/1.73 m² unless dialysis is initiated. 2

• The glucose-lowering efficacy of Jardiance decreases with declining renal function, but the cardiovascular and renal protective benefits—including hyperkalemia reduction—persist. 4

• In patients with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m²), Jardiance 25 mg provided statistically significant HbA1c reduction of -0.4% compared to placebo, though efficacy diminishes as eGFR approaches 30 mL/min/1.73 m². 4

Management Algorithm for Hyperkalemia in Patients on RAAS Inhibitors

When hyperkalemia develops in a diabetic patient taking ACE inhibitors or ARBs:

1. First-line intervention: Add Jardiance (if eGFR ≥20 mL/min/1.73 m²) rather than reducing or stopping the RAAS inhibitor. 2, 3

2. Second-line: Consider switching from ACE inhibitor to sacubitril/valsartan in heart failure patients, which reduces severe hyperkalemia risk by 27% (HR 1.37 for enalapril vs sacubitril/valsartan). 2, 3

3. Third-line: Add potassium binders (patiromer or sodium zirconium cyclosilicate) if hyperkalemia persists despite SGLT2 inhibitor therapy. 2, 3

4. Last resort: Reduce RAAS inhibitor dose rather than complete discontinuation, as withdrawal worsens cardiovascular and kidney outcomes. 2, 3

Monitoring Requirements

• Check serum potassium and renal function within 1-2 weeks of initiating Jardiance, particularly in patients with baseline eGFR <60 mL/min/1.73 m². 3

• For high-risk patients (CKD, diabetes, heart failure, on RAAS inhibitors), monitor potassium every 2-4 weeks initially, then monthly once stable. 2

• Serum creatinine and potassium should be monitored during treatment with ACE inhibitors, ARBs, or diuretics, particularly among patients with reduced glomerular filtration. 5

Critical Pitfalls to Avoid

• Never discontinue RAAS inhibitors reflexively when hyperkalemia develops; instead, add Jardiance or a potassium binder to maintain cardiovascular and renal protection. 2, 3

• Avoid combining ACE inhibitor + ARB + mineralocorticoid receptor antagonist (triple RAAS blockade), as this dramatically increases hyperkalemia risk without added benefit. 5

• Do not overlook insulin deficiency as a cause of hyperkalemia in diabetic patients; hyperglycemia itself causes potassium shifts, and insulin therapy will lower potassium levels. 2, 6

• Educate patients to avoid over-the-counter potassium supplements, potassium-based salt substitutes, high-potassium foods, and NSAIDs, which all increase hyperkalemia risk. 5

Volume Status Considerations

• Jardiance causes intravascular volume contraction, which may lead to symptomatic hypotension, particularly in patients with renal impairment, elderly patients, those with low baseline blood pressure, or those on diuretics. 4

• Assess volume status before initiating Jardiance and correct volume depletion if present; monitor for signs of hypotension after starting therapy. 4