How should I manage hyperkalemia (serum potassium 6 mmol/L) in an adult with type 2 diabetes on dapagliflozin (Farxiga) and metformin, hemoglobin A1c 11.2%, and estimated glomerular filtration rate 66 mL/min/1.73 m²?

Management of Hyperkalemia in a Patient with Type 2 Diabetes on Dapagliflozin and Metformin

Immediate Hyperkalemia Management

Stop any potassium-sparing medications immediately and treat the hyperkalemia urgently with standard protocols (calcium gluconate if ECG changes, insulin-dextrose, sodium polystyrene sulfonate, or dialysis if severe), then investigate the underlying cause. 1

• Serum potassium of 6.0 mmol/L constitutes severe hyperkalemia requiring immediate intervention to prevent life-threatening arrhythmias 1
• Check for ECG changes (peaked T-waves, widened QRS) and administer calcium gluconate 10% (10 mL IV over 2–3 minutes) if present to stabilize cardiac membranes 1
• Shift potassium intracellularly with regular insulin 10 units IV plus 25 g dextrose (if glucose <250 mg/dL), and consider nebulized albuterol 10–20 mg 1
• Remove excess potassium with sodium polystyrene sulfonate 15–30 g orally or 50 g rectally, or consider urgent hemodialysis if refractory 1

Medication Review and Adjustment

Continue both dapagliflozin and metformin without dose adjustment, as neither agent causes hyperkalemia; instead, systematically identify and discontinue the actual culprit medications. 1, 2

• Dapagliflozin should be maintained at 10 mg daily for cardiovascular and renal protection at eGFR 66 mL/min/1.73 m², as it reduces hyperkalemia risk rather than causing it 1, 2
• SGLT2 inhibitors like dapagliflozin actually reduce the risk of hyperkalemia and may facilitate the use of renin-angiotensin-aldosterone system (RAAS) blockers 2
• Metformin continuation is appropriate at eGFR 66 mL/min/1.73 m² without dose reduction; reduce to maximum 1000 mg/day only if eGFR falls to 30–44 mL/min/1.73 m² 1, 3

Identify the True Cause of Hyperkalemia

Systematically review for ACE inhibitors, ARBs, aldosterone antagonists (spironolactone, eplerenone), NSAIDs, potassium supplements, or salt substitutes—these are the likely culprits, not dapagliflozin or metformin. 1

• ACE inhibitors and ARBs are the most common medication-related causes of hyperkalemia in diabetic patients with CKD 1
• If the patient is on an ACE inhibitor or ARB, temporarily hold the agent until potassium normalizes, then restart at a reduced dose with close monitoring 1
• Aldosterone antagonists (spironolactone, eplerenone) markedly increase hyperkalemia risk and should be stopped if potassium >5.5 mmol/L 1
• NSAIDs impair renal potassium excretion and must be discontinued in patients with CKD and hyperkalemia 1
• Check for dietary potassium excess, potassium supplements, or potassium-containing salt substitutes 1

Renal Function Monitoring

Recheck eGFR and potassium within 1–2 weeks after dapagliflozin initiation or any medication change, as an expected transient eGFR dip of 2–5 mL/min/1.73 m² occurs but should not trigger discontinuation. 2, 4

• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² typically occurs within the first 2–4 weeks of dapagliflozin initiation, reflecting hemodynamic changes rather than kidney injury 2, 4
• This initial eGFR dip is not harmful and patients experiencing it actually have better long-term renal outcomes with slower eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) 2
• Monitor eGFR every 3–6 months when eGFR is 45–75 mL/min/1.73 m² 1, 3

Glycemic Control Optimization

The improvement from HbA1c 13.4% to 11.2% is encouraging but still far above target; intensify therapy by adding a GLP-1 receptor agonist (semaglutide, dulaglutide, or liraglutide) to achieve HbA1c <7%. 1, 5

• HbA1c 11.2% remains severely elevated and requires immediate treatment intensification to prevent metabolic decompensation and preserve beta-cell function 5
• Add a GLP-1 receptor agonist to the current metformin-dapagliflozin regimen, as this combination provides an additional 0.6–0.8% HbA1c reduction (up to 1.5% with semaglutide) 5
• GLP-1 receptor agonists cause weight loss (2–5 kg), have minimal hypoglycemia risk when not combined with sulfonylureas, and provide proven cardiovascular benefit 5
• If HbA1c remains >7% after 3 months of optimized triple therapy (metformin + dapagliflozin + GLP-1 RA), initiate basal insulin at 10 units daily or 0.1–0.2 units/kg 5

Cardiovascular and Renal Protection

Dapagliflozin provides critical cardiovascular and renal protection independent of glycemic control and must be continued even if eGFR declines below 45 mL/min/1.73 m². 1, 2, 6, 7

• Dapagliflozin reduces the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51–0.72) 6, 7
• Kidney-specific outcomes (sustained eGFR decline, ESKD, or renal death) improve by 44% (HR 0.56,95% CI 0.45–0.68) 6, 7
• Cardiovascular death or heart failure hospitalization decreases by 29% (HR 0.71,95% CI 0.55–0.92) 6, 7
• All-cause mortality is reduced by 31% (HR 0.69,95% CI 0.53–0.88) 6, 7
• These benefits persist at eGFR 25–75 mL/min/1.73 m² regardless of diabetes status 6, 7

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin because of hyperkalemia; SGLT2 inhibitors reduce rather than cause hyperkalemia 1, 2
• Do not stop dapagliflozin if eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite reduced glycemic efficacy 1, 2
• Do not attribute hyperkalemia to metformin or dapagliflozin without first excluding RAAS blockers, aldosterone antagonists, NSAIDs, and dietary sources 1
• Do not accept HbA1c 11.2% as adequate control; this level requires immediate intensification to prevent complications 1, 5
• Do not reduce metformin dose at eGFR 66 mL/min/1.73 m²; dose reduction is only needed when eGFR falls to 30–44 mL/min/1.73 m² 1, 3