What is the management of euglycemic ketoacidosis secondary to Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

From the Guidelines

Management of euglycemic diabetic ketoacidosis (euDKA) secondary to SGLT2 inhibitors requires immediate discontinuation of the SGLT2 inhibitor and initiation of standard DKA treatment despite normal blood glucose levels, as recommended by the most recent guidelines 1.

Key Considerations

• Patients should receive IV fluids, typically 0.9% saline at 15-20 mL/kg/hr initially, then adjusted based on hydration status.
• IV insulin therapy should be initiated with a regular insulin bolus of 0.1 units/kg followed by continuous infusion at 0.1 units/kg/hr.
• Electrolyte replacement, particularly potassium to maintain levels between 4-5 mEq/L, is crucial.
• Dextrose-containing fluids (D5W or D10W) should be started early, even with normal glucose levels, to prevent hypoglycemia while continuing insulin to clear ketones.

Monitoring and Education

• Frequent monitoring of glucose, electrolytes, and ketones is essential, with insulin continued until ketosis resolves (anion gap normalizes and ketones clear) 1.
• Patients should be educated to temporarily stop SGLT2 inhibitors during periods of fasting, surgery, or acute illness, and to seek immediate medical attention if they develop symptoms of ketoacidosis even with normal glucose readings.
• The underlying trigger for euDKA should be identified and addressed, which commonly includes infection, surgery, reduced insulin doses, or inadequate carbohydrate intake.

Prevention Strategies

• Daily hygiene to keep the genital area clean and dry can help prevent genital mycotic infections, a known complication of SGLT2 inhibitors 1.
• Diuretic dose reduction in patients at risk for hypovolemia and implementation of a sick day protocol can also help mitigate the risk of euDKA.
• Patients should be advised to monitor for signs of volume depletion, such as orthostatic lightheadedness, and to contact their clinician if these occur 1.

From the Research

Management of Euglycemic Ketoacidosis

The management of euglycemic ketoacidosis secondary to Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors involves several key considerations:

• Prompt recognition and diagnosis of euglycemic diabetic ketoacidosis (EDKA) is crucial, as it can present with nonspecific symptoms such as nausea, vomiting, fatigue, and altered mental status 2.
• Patients with EDKA associated with SGLT2i use typically require insulin infusion, with a median duration of 18.77 hours 2.
• It is essential to monitor for potential complications, such as hypoglycemia and hypokalemia, while on insulin infusion 2.
• Time to resolution of metabolic acidosis is approximately 23.82 hours 2.
• In some cases, patients may require treatment with intravenous glucose administration and encouragement of oral glucose intake, particularly if ketoacidosis is triggered by reduced oral nutrition intake 3.
• The use of SGLT2 inhibitors can promote lipolysis and ketogenesis, even in the absence of hyperglycemia, and patients should be aware of the risks of EDKA, especially during periods of carbohydrate deficiency, volume depletion, and stress 4, 5.

Key Considerations for SGLT2 Inhibitor Therapy

• Appropriate holding parameters and timely diagnosis of EDKA are critical to ensure safe SGLT2 inhibitor therapy 4.
• Patients should be educated on the risks of EDKA and the importance of seeking medical attention if symptoms occur 5.
• The pharmacologic effects of SGLT2 inhibitors can persist beyond several half-lives of elimination, and patients should be monitored closely for signs of EDKA, even after discontinuation of the medication 4.