How should I manage a patient with severe hyperglycemia (294 mg/dL) and hyperkalemia (6 mEq/L) who is taking dapagliflozin (Farxiga) and metformin, with an estimated glomerular filtration rate of 66 mL/min/1.73 m²?

Immediate Management of Severe Hyperglycemia and Hyperkalemia in a Patient on Dapagliflozin and Metformin

Stop dapagliflozin immediately and initiate insulin therapy for glucose 294 mg/dL; discontinue metformin at GFR 66 mL/min/1.73 m² only if acute illness or volume depletion is present, otherwise continue with increased monitoring. 1, 2, 3

Immediate Actions for Hyperglycemia (294 mg/dL)

Initiate insulin therapy immediately because blood glucose ≥300 mg/dL (or A1C >10%) warrants insulin regardless of background therapy, especially when symptoms of hyperglycemia are present. 1 Your patient at 294 mg/dL is approaching this threshold and likely symptomatic.

• Start basal insulin (e.g., glargine 10 units subcutaneously daily) or consider rapid-acting insulin if the patient is acutely ill. 1
• Once glucose toxicity resolves over days to weeks, you can simplify the regimen and potentially transition back to noninsulin agents. 1
• GLP-1 receptor agonists (semaglutide, dulaglutide, or liraglutide) are highly effective alternatives that can be added or substituted once acute hyperglycemia is controlled, with lower hypoglycemia risk than insulin. 1

Critical Decision: Stop Dapagliflozin Immediately

Discontinue dapagliflozin now due to the combination of severe hyperglycemia and hyperkalemia, which creates high risk for euglycemic diabetic ketoacidosis (DKA). 4, 5

• SGLT2 inhibitors like dapagliflozin cause euglycemic DKA—a life-threatening condition presenting with nausea, vomiting, abdominal pain, dyspnea, and lethargy despite blood glucose <250 mg/dL. 4, 5
• Precipitating factors include acute illness, poor oral intake, fasting, infection, and volume depletion—any of which may be present in your patient given the severe hyperglycemia. 4, 5
• Check serum or urine ketones and arterial blood gas immediately to rule out DKA, even though glucose is only 294 mg/dL. 4, 5
• Do not restart dapagliflozin until glucose is controlled, ketones are negative, and any acute illness has resolved. 4, 5

Hyperkalemia Management (Potassium 6 mEq/L)

Treat hyperkalemia urgently with standard protocols while investigating the cause:

• Administer calcium gluconate 10% (10 mL IV over 2–3 minutes) for cardiac membrane stabilization if ECG shows peaked T-waves or QRS widening. [@general medicine knowledge@]
• Give insulin (10 units regular IV) plus dextrose (25 g IV) to shift potassium intracellularly—this also helps lower glucose. [@general medicine knowledge@]
• Add inhaled albuterol (10–20 mg nebulized) for additional potassium lowering. [@general medicine knowledge@]
• Consider sodium polystyrene sulfonate or patiromer for sustained potassium removal if renal function is impaired. [@general medicine knowledge@]
• Investigate causes: Check for acute kidney injury, medications (ACE inhibitors, ARBs, potassium-sparing diuretics), dietary potassium excess, or hemolysis (repeat potassium if hemolyzed sample suspected). [@general medicine knowledge@]

Metformin Management at GFR 66 mL/min/1.73 m²

Continue metformin at current dose because GFR 66 mL/min/1.73 m² is well above the safety threshold, but increase monitoring frequency and assess for acute illness. 2, 3, 6

Current GFR 66 mL/min/1.73 m² (Safe Range)

• Metformin is safe and should be continued at standard doses (up to 2000–2550 mg daily) when eGFR ≥60 mL/min/1.73 m². 2, 3
• Increase eGFR monitoring to every 3–6 months (not annually) because the patient's GFR is approaching the 60 mL/min/1.73 m² threshold. 2, 3, 6
• Monitor vitamin B12 levels if the patient has been on metformin for >4 years, as approximately 7% develop deficiency. 2, 3

Temporary Metformin Discontinuation Criteria

Hold metformin immediately if any of the following are present:

• Acute illness causing volume depletion (sepsis, severe diarrhea, vomiting, dehydration). 2, 3, 6
• Hospitalization with elevated acute kidney injury risk. 2, 3
• Planned iodinated contrast imaging in patients with liver disease, alcoholism, or heart failure—hold at time of procedure and recheck eGFR 48 hours later before restarting. 2, 3

Future GFR Thresholds

• GFR 45–59 mL/min/1.73 m²: Continue current dose; monitor every 3–6 months. 2, 3, 6
• GFR 30–44 mL/min/1.73 m²: Reduce dose by 50% (maximum 1000 mg daily); monitor every 3–6 months. 2, 3, 6
• GFR <30 mL/min/1.73 m²: Discontinue immediately (absolute contraindication due to lactic acidosis risk). 2, 3, 6

When to Restart or Add SGLT2 Inhibitor

Do not restart dapagliflozin until:

• Glucose is controlled (A1C <9%, fasting glucose <180 mg/dL). 1
• Ketones are negative and no acute illness is present. 4, 5
• Potassium is normalized (<5.0 mEq/L). [@general medicine knowledge@]

Once stable, strongly consider restarting dapagliflozin because:

• SGLT2 inhibitors provide cardiovascular and renal protection independent of glucose lowering, reducing heart failure hospitalization and CKD progression. 1, 2
• Dapagliflozin can be initiated and continued at GFR ≥25 mL/min/1.73 m² for cardiorenal benefit. 1, 2, 7, 8
• Even if GFR falls below 45 mL/min/1.73 m² (where glucose-lowering efficacy declines), continue dapagliflozin for cardiovascular and renal protection. 1, 2, 8
• Expect a transient 3–5 mL/min/1.73 m² eGFR dip in the first 4 weeks, which is hemodynamic and reversible. 6, 9

Alternative Glucose-Lowering Therapies

If dapagliflozin cannot be restarted or additional therapy is needed:

• First-line: Add a GLP-1 receptor agonist (semaglutide 0.5–1 mg weekly, dulaglutide 0.75–1.5 mg weekly, or liraglutide 1.2–1.8 mg daily) for proven cardiovascular benefit and superior glucose lowering without hypoglycemia risk. 1, 2, 6
• Second-line: DPP-4 inhibitors with renal dosing (sitagliptin 100 mg daily at GFR >50 mL/min/1.73 m²; linagliptin requires no adjustment). 2, 6
• Avoid sulfonylureas (especially glyburide) due to high hypoglycemia risk in kidney disease; if necessary, use only glipizide at low doses (2.5 mg daily). 2, 6

Common Pitfalls to Avoid

• Do not continue dapagliflozin during acute hyperglycemia with possible ketosis—this is the most dangerous error and can cause fatal euglycemic DKA. 4, 5
• Do not discontinue metformin prematurely at GFR 66 mL/min/1.73 m²—this is well above the 30 mL/min/1.73 m² contraindication threshold. 2, 3, 6
• Do not forget to check ketones—euglycemic DKA presents with glucose <250 mg/dL but severe acidosis and ketosis. 4, 5
• Do not delay insulin initiation—glucose 294 mg/dL requires immediate insulin therapy per guidelines. 1
• Do not ignore the hyperkalemia—this requires urgent treatment and investigation for underlying causes. [@general medicine knowledge@]