How to reduce diabetic ketoacidosis (DKA) risk in patients on Empagliflozin (empagliflozin)?

From the Guidelines

To reduce the risk of diabetic ketoacidosis (DKA) in patients on empagliflozin, it is recommended to temporarily discontinue empagliflozin at least 3-4 days before planned surgical procedures or during acute illness, especially when food intake is reduced, as suggested by the most recent guidelines 1.

Key Recommendations

• Ensure adequate hydration by encouraging patients to drink plenty of fluids, particularly during illness or when physical activity is increased.
• Monitor ketone levels regularly, especially during illness, using blood ketone meters rather than urine testing for more accurate results, as emphasized in the 2022 clinical practice guideline for diabetes management in chronic kidney disease 1.
• Maintain sufficient carbohydrate intake (at least 100g daily) while on empagliflozin, particularly during periods of reduced caloric intake.
• Consider temporary insulin supplementation during illness or fasting states to suppress ketogenesis, as noted in the consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.
• Educate patients about eDKA symptoms including nausea, vomiting, abdominal pain, fatigue, and rapid breathing, emphasizing that blood glucose may remain near normal despite ketoacidosis.

Rationale

The use of SGLT2 inhibitors like empagliflozin increases the susceptibility to diabetic ketoacidosis, particularly when other risk factors or situations occur, such as insulin pump malfunctions, significant reduction in insulin doses, and nutritional intake plans with prolonged periods of fasting or carbohydrate restriction, as discussed in the 2025 standards of care in diabetes 1. Regular monitoring of ketone levels and maintaining adequate hydration and carbohydrate intake can help mitigate this risk. Temporary discontinuation of empagliflozin during acute illness or planned surgical procedures can also reduce the risk of DKA, as suggested by the practical approach to initiating SGLT2 inhibitors in patients with type 2 diabetes and chronic kidney disease 1.

Important Considerations

• Patients with type 1 diabetes and those requiring insulin are at particular risk of eDKA, and close monitoring and education are essential, as noted in the 2022 clinical practice guideline for diabetes management in chronic kidney disease 1.
• The risk of genital mycotic infections is higher with SGLT2 inhibitors, and daily hygienic measures may lessen this risk, as discussed in the consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1.
• Regular follow-up and assessment of adverse effects are crucial when initiating SGLT2 inhibitors, as emphasized in the practical provider guide to initiating SGLT2 inhibitors in patients with type 2 diabetes and CKD 1.

From the Research

Reducing Diabetic Ketoacidosis (DKA) Risk in Patients on Empagliflozin

To reduce the risk of diabetic ketoacidosis (DKA) in patients on empagliflozin, several measures can be taken:

• Monitor patients closely for signs and symptoms of DKA, such as nausea, vomiting, and confusion 2, 3, 4, 5
• Be aware of the risk of euglycemic DKA, which can occur even with normal or mildly elevated blood glucose levels 3, 4, 5
• Educate patients on the importance of proper insulin administration and injection techniques to prevent complications such as improper insulin delivery and dose reduction 3
• Consider measuring C-peptide and anti-GAD antibody levels to help differentiate between type 1 and type 2 diabetes, as management strategies vary significantly 3
• Advise patients to avoid low-carbohydrate diets while taking empagliflozin, as this can increase the risk of euglycemic DKA 6
• Discontinue empagliflozin if DKA is suspected or confirmed, and initiate treatment with intravenous fluids and insulin infusions 2, 4, 5

Patient Education and Awareness

Patient education and awareness are crucial in reducing the risk of DKA:

• Inform patients about the potential side effects of empagliflozin, including the risk of DKA 3, 6
• Educate patients on how to recognize the signs and symptoms of DKA and when to seek medical attention 2, 3, 4, 5
• Emphasize the importance of proper medication management, including taking empagliflozin as directed and not reducing insulin doses without consulting a healthcare provider 3

Healthcare Provider Vigilance

Healthcare providers should be vigilant for DKA in patients on empagliflozin:

• Be aware of the risk of euglycemic DKA and consider this diagnosis in patients with unexplained metabolic acidosis 3, 4, 5
• Monitor patients closely for signs and symptoms of DKA, particularly in patients with type 1 diabetes or those who have reduced their insulin doses 2, 3
• Discontinue empagliflozin and initiate treatment with intravenous fluids and insulin infusions if DKA is suspected or confirmed 2, 4, 5