What are the clinical presentation and management of a patient with diabetic ketoacidosis (DKA) due to adverse effects of Farxiga (dapagliflozin)?

Clinical Case: Euglycemic Diabetic Ketoacidosis Due to Farxiga (Dapagliflozin)

Farxiga (dapagliflozin) can cause euglycemic diabetic ketoacidosis (eDKA), a life-threatening condition characterized by ketoacidosis with normal or only mildly elevated blood glucose levels, requiring prompt recognition and treatment despite the absence of marked hyperglycemia. 1, 2

Clinical Presentation

Patient Profile

• 61-year-old female with type 2 diabetes
• Recently started on dapagliflozin (2 weeks prior)
• Current medications: metformin, glibenclamide, and dapagliflozin
• Precipitating factor: poor oral intake for 1 week due to severe toothache

Presenting Symptoms

• Body weakness and lethargy
• Dyspnea
• Nausea and vomiting
• Mild abdominal pain
• Clinical dehydration with dry mucous membranes
• Possible weight loss (as seen in similar cases)

Laboratory Findings

• Blood glucose: 180 mg/dL (only mildly elevated)
• Arterial blood gas: severe metabolic acidosis
• Elevated anion gap
• Elevated serum ketones
• Positive urine ketones
• Normal serum lactate levels
• Possible electrolyte abnormalities (particularly potassium)
• Possible elevated hematocrit due to dehydration

Diagnosis

The diagnosis of eDKA due to dapagliflozin is based on:

• Metabolic acidosis (arterial pH <7.3)
• Serum bicarbonate <15 mEq/L
• Elevated ketones in blood and urine
• Blood glucose <250 mg/dL (typically 180-200 mg/dL)
• Recent initiation of SGLT2 inhibitor (dapagliflozin)
• Presence of precipitating factor (poor oral intake) 3, 2, 4

Management

Immediate Management

1. Admit to ICU or monitored setting for close observation 3, 2

2. Fluid resuscitation:

   • Isotonic saline at 15-20 ml/kg/hour for the first hour
   • Then transition to balanced crystalloids at 4-14 ml/kg/hour based on hydration status 3
   • Include dextrose-containing fluids to prevent hypoglycemia 3

3. Insulin therapy:

   • Regular insulin continuous IV infusion at 0.1 units/kg/hour (no initial bolus)
   • Continue until resolution of ketoacidosis 3, 2

4. Electrolyte management:

   • Monitor potassium levels closely
   • Begin potassium replacement when serum K+ <5.5 mEq/L with adequate urine output
   • Add 20-30 mEq/L potassium (2/3 KCl and 1/3 KPO₄) to IV fluids 3

5. Glucose monitoring:

   • Check blood glucose hourly
   • Add dextrose to IV fluids when glucose falls below 200 mg/dL to prevent hypoglycemia while continuing insulin to clear ketosis 3, 4

Monitoring

• Vital signs, neurological status, blood glucose: hourly
• Electrolytes, BUN, creatinine, venous pH: every 2-4 hours
• Fluid input/output: hourly 3

Resolution Criteria

DKA is considered resolved when:

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3 3

Transition to Subcutaneous Insulin

• Administer basal insulin 2-4 hours before discontinuing IV insulin to prevent rebound hyperglycemia
• Consider low-dose basal insulin analog in addition to IV insulin 3

Discharge Planning and Prevention

1. Medication adjustments:

   • Permanently discontinue dapagliflozin 2
   • Adjust other diabetes medications as needed

2. Patient education:

   • Diabetes self-management
   • Glucose monitoring
   • Sick-day management (never suspend insulin during illness)
   • Recognition of eDKA symptoms
   • When to seek medical attention 3

3. Follow-up:

   • Schedule follow-up appointment prior to discharge
   • Ensure ongoing diabetes care management 3

Important Considerations and Pitfalls

• Diagnostic challenge: eDKA is easily missed due to absence of marked hyperglycemia 2, 4
• High risk situations: Poor oral intake, surgery, alcohol use, infection can precipitate eDKA in patients on SGLT2 inhibitors 4
• Medication awareness: In the DECLARE trial, DKA was reported in 27 out of 8574 dapagliflozin-treated patients compared to 12 out of 8569 placebo patients 1
• Laboratory monitoring: Watch for decreases in serum bicarbonate, which can be an early sign of ketoacidosis in patients on dapagliflozin 1
• Complications to monitor: Cerebral edema, hypoglycemia, hypokalemia, and fluid overload 3

This case highlights the importance of considering eDKA in any patient on SGLT2 inhibitors presenting with nausea, vomiting, abdominal pain, dyspnea, or lethargy, even with normal or only slightly elevated blood glucose levels.