Euglycemic DKA in Patients Taking SGLT2 Inhibitors

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
The American College of Cardiology recommends that patients should be informed about the risk of euglycemic DKA and advised to seek immediate care if symptoms develop, such as nausea, vomiting, abdominal pain, and generalized weakness 4
Several case reports document euglycemic DKA in patients without diabetes mellitus who were taking SGLT2 inhibitors 2

Reduced oral intake or fasting can precipitate euglycemic DKA in patients taking SGLT2 inhibitors 3
Surgery or invasive procedures can also increase the risk of euglycemic DKA in these patients 1
Dehydration is a precipitating factor for euglycemic DKA in patients taking SGLT2 inhibitors 3
Excessive alcohol intake can also contribute to the development of euglycemic DKA in patients taking SGLT2 inhibitors 3

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, 2
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, 2
Emergency surgery carries a higher risk of DKA than elective surgery (1.1% vs. 0.17%) 1, 2

The American College of Cardiology recommends avoiding substantial initial reductions in insulin dose (>20%) after initiation of SGLT2 inhibitors 4
For perioperative management, SGLT2 inhibitors should be omitted the day before and the day of a procedure 2
Maintaining adequate hydration and avoiding prolonged fasting periods can help prevent euglycemic DKA in patients taking SGLT2 inhibitors 2
Monitoring glucose and ketone levels during high-risk periods is crucial for early detection of euglycemic DKA 2

Patients on complex insulin regimens or with a history of labile blood glucose should have SGLT2 inhibitors initiated in collaboration with diabetes care providers, as recommended by the American College of Cardiology 4
Approximately 5-10% of adult-onset diabetes is late-onset type 1; these patients have an increased risk of DKA 4
The risk of euglycemic DKA exists as a continuum rather than having a defined threshold when it will not occur 2