Management of Empagliflozin-Induced Ketoacidosis
Immediately discontinue empagliflozin, initiate intravenous insulin infusion with dextrose-containing fluids, and provide aggressive fluid resuscitation to treat the euglycemic diabetic ketoacidosis (euDKA), which typically resolves within 24 hours with appropriate management. 1, 2, 3
Immediate Recognition and Diagnosis
The diagnostic challenge with empagliflozin-induced ketoacidosis is that blood glucose levels are often normal or only mildly elevated (<200 mg/dL), making this easily missed in the emergency setting. 1, 2
Key diagnostic criteria to confirm:
- Arterial blood pH <7.35 with high anion gap metabolic acidosis 2, 3
- Elevated serum ketones and positive urine ketones 2, 3
- Blood glucose typically <250 mg/dL (often 150-200 mg/dL range) 2, 3, 4
- Normal serum lactate to exclude lactic acidosis 2
Acute Management Protocol
Step 1: Discontinue Empagliflozin Permanently
Stop empagliflozin immediately and do not restart - this is a contraindication to future use. 2, 3, 4, 5, 6
Step 2: Intensive Care Unit Admission
Admit to ICU for close monitoring given the potential for rapid deterioration and complications including acute kidney injury, cerebral edema, acute respiratory distress syndrome, and shock. 3, 6
Step 3: Fluid Resuscitation
Initiate aggressive intravenous fluid resuscitation as volume depletion is a key component of the pathophysiology. 2, 3, 6
Step 4: Insulin and Dextrose Therapy
Start intravenous insulin infusion with dextrose-containing fluids - this is critical because unlike typical DKA, these patients need dextrose supplementation due to relatively normal glucose levels. 2, 3, 6
The dextrose prevents hypoglycemia while insulin suppresses ketogenesis. 6
Step 5: Serial Monitoring
Obtain serial arterial blood gases every 2-4 hours to monitor resolution of acidosis, along with frequent electrolyte panels and anion gap calculations. 2, 3
Resolution typically occurs within 24 hours with normalization of pH, closure of anion gap, and clearance of serum ketones. 2, 3, 6
Prevention Strategies for Future SGLT2 Inhibitor Use
If considering any SGLT2 inhibitor in other patients, implement these safeguards:
Preoperative Management
Discontinue empagliflozin 3 days before any elective or anticipated invasive procedures (4 days for ertugliflozin) to minimize perioperative ketoacidosis risk. 1, 7, 8
High-Risk Situations Requiring Temporary Discontinuation
Stop empagliflozin during:
- Acute illness or infection 7, 8
- Reduced caloric intake or fasting states (including ketogenic diets) 7, 8, 3
- Volume depletion or dehydration 7, 8
- Alcohol consumption 1, 7
- Any surgical procedure 7, 8, 6
Patient Education
Counsel patients to seek immediate medical attention if they develop:
- Nausea, vomiting, or abdominal pain 1, 2, 5
- Dyspnea or shortness of breath 2, 3, 5
- Generalized weakness or lethargy 3, 5
- Malaise 1
Critical teaching point: Warn patients that home glucose readings may be falsely reassuring (appearing normal or only mildly elevated) despite serious ketoacidosis. 5
Special Populations at Higher Risk
Exercise extreme caution or avoid empagliflozin in:
- Patients with insulin deficiency (particularly type 1 diabetes, though empagliflozin is not approved for this indication) 7, 4
- Elderly patients 7, 8
- Those with reduced renal function 7, 8
- Patients on concurrent diuretics 7, 8
- Those with low systolic blood pressure (<100 mmHg) 1, 7, 8
Clinical Pitfalls to Avoid
The most common error is attributing symptoms to other conditions (such as viral illness, MS exacerbation, or simple dehydration) and missing the diagnosis due to normal glucose levels. 5
Do not delay treatment while pursuing alternative diagnoses - if a patient on empagliflozin presents with unexplained metabolic acidosis, check ketones immediately regardless of glucose level. 1, 2, 5
Do not use standard DKA protocols without modification - these patients require dextrose-containing fluids from the outset, unlike typical hyperglycemic DKA. 6