Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium–Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction

Objective: Ketoacidosis induced by sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis. 

Research design and Methods: We describe the first two case reports of severe nondiabetic ketoacidosis after initiation of an SGLT2i for the treatment of heart failure with reduced ejection fraction, and we describe the management strategies employed and implication for the pathophysiology of SGLT2i-associated ketoacidosis. 

Results: Each individual presented with ketoacidosis triggered by reduced oral nutrition intake. For both individuals, ketoacidosis resolved with intravenous glucose administration, encouragement of consumption of oral glucose-containing fluid, and minimal insulin administration. 

Conclusions: These two cases demonstrate that SGLT2i-associated ketoacidosis is possible in individuals without diabetes.