Hyperglycemic, high anion-gap metabolic acidosis in patients receiving SGLT-2 inhibitors for diabetes management

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a class of antidiabetic medications that improve glycemic control via inhibiting the reabsorption of filtered glucose and are approved for use in type 2 diabetes (T2DM). These drugs have recently been associated with euglycemic diabetic ketoacidosis (DKA). An increasing number of cases of SGLT-2i-associated DKA have occurred in patients with T2DM. Herein, we describe five episodes of hyperglycemic DKA in four type 2 diabetes patients receiving SGLT-2i therapy. Risk for ketoacidosis in our case series was mediated predominately by reduction of insulin dose and insulinopenia. None of the patients reported a history of low carbohydrate diet or alcohol use, and all but one patient had negative glutamic acid decarboxylase antibodies. Resolution of DKA in SGLT-2i treated patients took longer than for T1DM patients with DKA based on literature data. The mechanisms by which SGLT-2i are associated with ketoacidosis are not fully understood and likely involve hyperglucagonemia and other factors. Further studies are needed to elucidate the precise mechanism.