Figure 1.

Proposed role of sodium-glucose cotransporter 2 (SGLT2) inhibition in euglycemic diabetic ketoacidosis (eDKA). Classic DKA results from insulin deficiency (absolute or relative) and concurrent increase in counter-regulatory hormones leading to ketosis, hyperglycemia, and osmotic diuresis. In contrast, SGLT2 inhibitor therapy in a well-compensated individual at baseline causes glucosuria, mild volume depletion, and lower serum glucose levels, associated with decreased insulin secretion (green box). During times of intercurrent illness and/or metabolic stress (eg, surgery or gastrointestinal illness), decreased carbohydrate intake coupled with lower serum glucose levels can further depress insulin secretion. This can ultimately lead to eDKA (red box). ∗Possible pathways of carbohydrate deficiency and causes of insulinopenia. Abbreviations: BP, blood pressure; PO, oral.