SGLT2 Inhibitor-Associated Ketoacidosis vs Type 1 Diabetes-Associated Ketoacidosis

The pathophysiology of sodium-glucose cotransporter 2 inhibitor (SGLT2i)–associated ketoacidosis (DKA) differs from type 1 diabetes (T1D) DKA. T1D DKA is driven by absolute insulin deficiency, leading to ketosis and hyperglycemia. In contrast, SGLT2i DKA occurs due to reduction in plasma glucose (PG) from urinary glucose losses, which reduces insulin secretion and stimulates glucagon secretion, leading to ketosis. Accordingly, PG levels in SGLT2i DKA are often normal or mildly elevated. The implication is that glycemia and ketosis are less closely linked than in T1D DKA. Despite these differences, the American Association of Clinical Endocrinologists and American College of Endocrinology recommends treatment with the same protocols as T1D.4 This may result in hypoglycemia when patients receive fixed-dose insulin infusion or inadequate insulin dosing and reduced ketone clearance when patients receive dynamic insulin infusions.