Empagliflozin and Risk of Diabetic Ketoacidosis in Type 2 Diabetes
Empagliflozin carries a significant risk of euglycemic diabetic ketoacidosis (euDKA) in patients with type 2 diabetes, particularly during periods of metabolic stress such as illness, surgery, or reduced food intake, and requires careful monitoring and patient education to prevent this potentially life-threatening complication. 1, 2
Risk of Diabetic Ketoacidosis with Empagliflozin
- Empagliflozin, like other SGLT2 inhibitors, is associated with euglycemic diabetic ketoacidosis (euDKA), a serious condition that can occur even when blood glucose levels are below 250 mg/dL 2
- EuDKA is particularly challenging to diagnose due to the absence of marked hyperglycemia, which can lead to delayed recognition and treatment 3, 4
- Fatal cases of ketoacidosis have been reported in patients taking empagliflozin 2
Predisposing Risk Factors for DKA
- Insulin deficiency (rare in type 2 diabetes but possible) 1
- Reduced caloric intake due to illness or fasting 1
- Acute illness or infection 1, 2
- Surgical procedures 1, 5
- Alcohol consumption 1, 2
- Volume depletion 1
- Following ketogenic diets 4
- Pancreatic disorders suggesting insulin deficiency 2
Clinical Presentation of Empagliflozin-Associated DKA
- Patients may present with nausea, vomiting, abdominal pain, and shortness of breath 2, 3
- Generalized weakness, malaise, and lethargy are common symptoms 3, 4
- High anion gap metabolic acidosis with blood glucose levels that may be only mildly elevated or even normal 4, 6
- Elevated ketones in blood and positive ketones in urine 3
- Dehydration is often present 3
Prevention Strategies
- Discontinue empagliflozin 3-4 days before scheduled surgery 1
- Temporarily discontinue during critical illness 1
- Temporarily discontinue during prolonged fasting 1
- Implement sick-day planning and education for patients 1
- Assess for factors predisposing to ketoacidosis before initiating therapy 2
- Monitor for ketoacidosis in vulnerable patients 1
Management of Empagliflozin-Associated DKA
- Prompt discontinuation of empagliflozin if DKA is suspected 2
- Immediate evaluation and treatment of suspected cases 2
- Standard DKA protocol with intravenous fluids and insulin infusion 3, 4
- Addition of dextrose may be required due to lower blood glucose levels 4
- Close monitoring until resolution of acidosis and clearance of ketones 3
Important Clinical Considerations
- Euglycemic DKA can recur even days after the last dose of empagliflozin due to its long-lasting effects 5
- Persistent glucosuria and ketonuria may continue for up to 11 days after discontinuation 5
- Empagliflozin is contraindicated in patients with type 1 diabetes 2
- Empagliflozin is not recommended for the treatment of diabetic ketoacidosis 2
- Consider monitoring for ketones in patients at high risk, even with normal blood glucose levels 3
Special Populations at Higher Risk
- Patients with reduced renal function 1
- Elderly patients 1
- Patients on diuretics 1
- Patients with low systolic blood pressure 1
- Surgical patients 5, 7
- Patients with intercurrent illness 1, 7
While empagliflozin offers significant cardiovascular and renal benefits for patients with type 2 diabetes 1, the risk of euglycemic DKA requires vigilance from both healthcare providers and patients. Early recognition of symptoms and prompt treatment are essential to prevent serious complications from this potentially life-threatening condition.