Euglycemic DKA in Patients Taking SGLT2 Inhibitors with Normal Insulin Levels
Yes, patients with normal insulin levels taking SGLT2 inhibitors can develop euglycemic diabetic ketoacidosis (DKA). 1 This risk exists even in individuals without diabetes mellitus who have sufficient baseline insulin levels.
Mechanism and Risk
- SGLT2 inhibitors lower glucose concentrations, altering the insulin/glucagon ratio and predisposing patients to ketosis, regardless of their baseline insulin status 1
- When physiological stress occurs, counterregulatory hormones drive hyperketonaemia, potentially leading to euglycemic DKA 1
- Until recently, it was believed that people without diabetes had sufficient insulin to prevent significant ketosis, but recent publications have challenged this assumption 1
- Several case reports document euglycemic DKA in patients without diabetes mellitus who were taking SGLT2 inhibitors 1
Diagnostic Challenges
- Euglycemic DKA presents with normal or minimally elevated glucose levels (<200 mg/dL or <11.0 mmol/L), making diagnosis difficult 1, 2
- The condition is characterized by high anion gap metabolic acidosis, elevated serum and urine ketones, with serum glucose <250 mg/dL 3
- The absence of hallmark symptoms like hyperglycemia, polyuria, and polydipsia often leads to delayed diagnosis 4, 5
Precipitating Factors
- Reduced oral intake or fasting 1, 4
- Major acute illness 4
- Surgery or invasive procedures 1, 6
- Insulin reduction or omission 1, 6
- Dehydration 1
- Excessive exercise 6
- Low-carbohydrate diets 6
- Excessive alcohol intake 1, 6
- Chronic pancreatitis 4
Incidence and Risk Comparison
- The risk of perioperative DKA is higher in patients taking SGLT2 inhibitors compared to those not taking them (1.02 vs. 0.69 per 1000 patients) 1
- In non-operative settings, DKA incidence is greater in patients with diabetes mellitus than those without (1 in 339 vs. 1 in 15,592) 1
- Emergency surgery carries a higher risk of DKA than elective surgery (1.1% vs. 0.17%) 1
Prevention Strategies
- Patients should be informed about the risk of euglycemic DKA and advised to seek immediate care if symptoms develop (nausea, vomiting, abdominal pain, generalized weakness) 1
- Avoid substantial initial reductions in insulin dose (>20%) after initiation of SGLT2 inhibitors 1
- For perioperative management, SGLT2 inhibitors should be omitted the day before and the day of a procedure 1
- Maintain adequate hydration and avoid prolonged fasting periods 1
- Monitor glucose and ketone levels during high-risk periods 1
- Consider glucose-containing intravenous fluids during unavoidable prolonged fasting 1
Management of Suspected Cases
- All SGLT2 inhibitor-treated patients presenting with signs or symptoms of DKA should be investigated for DKA, especially if euglycemic 6
- If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped immediately 6
- Treatment includes intravenous insulin, dextrose-containing fluids, and electrolyte replacement 5
Special Considerations
- Patients on complex insulin regimens or with a history of labile blood glucose should have SGLT2 inhibitors initiated in collaboration with diabetes care providers 1
- Approximately 5-10% of adult-onset diabetes is late-onset type 1; these patients have an increased risk of DKA 1
- The risk of euglycemic DKA exists as a continuum rather than having a defined threshold when it will not occur 1
In conclusion, the evidence clearly demonstrates that euglycemic DKA can occur in patients with normal insulin levels who are taking SGLT2 inhibitors. Healthcare providers should maintain a high index of suspicion for this condition in any patient on SGLT2 inhibitors presenting with symptoms suggestive of DKA, regardless of their glucose levels or diabetes status.