Sodium–Glucose Cotransporter 2 Inhibitor–Associated Prolonged Euglycemic Diabetic Ketoacidosis in Type 2 Diabetes: A Case Report and Literature Review

Background

Sodium–glucose cotransporters (SGLTs) are present in the kidney, gut, and heart. SGLT2 mediates kidney glucose reabsorption predominately through the proximal convoluted tubule. Thus, SGLT2 inhibitors, a novel class of antihyperglycemic medications, enhance glucose excretion in the urine and effectively lower glucose levels in the circulation (1). Because SGLT2 receptors work in a glucose-dependent manner, a higher glycemic load increases the effect of SGLT2 inhibitors and potentiates glucose lowering irrespective of insulin action. Furthermore, due to the high sodium gradient across the membrane of the proximal convoluted tubule, glucose is actively transported with sodium by the SGLT2 receptor into the tubular cells and is later passively reabsorbed (2–4). In addition to their role in diabetes, SGLT2 inhibitors have recently been linked to weight loss and blood pressure reduction, thought to be due to osmotic diuresis (5). More importantly, SGLT2 inhibitors have been shown to improve cardiovascular (CV) physiology and reduce both CV events and all-cause mortality independent of glucose lowering (6–8).

SGLT2 inhibitors increase glucosuria, making the urinary tract a favorable medium for bacterial and fungal growth and, in turn, increasing the incidence of both geni- tourinary and vaginal yeast infections (9). Hypoglycemia is fairly uncommon with these drugs (4). Drug-drug interactions are rarely reported with SGLT2 inhibitors; therefore, the doses of such medications need not be altered when used with other hypoglycemic agents (4,10). A recent meta-analysis exploring the potential interference of SGLT2 inhibitors with calcium and phosphate concentrations in the blood showed no increase in the risk of bone fracture in patients with type 2 diabetes (11). However, with regard to the adverse events observed with the SGLT2 inhibitors, euglycemic diabetic ketoacidosis (DKA), a serious and life-threatening complication with plasma glucose <200 mg/dL, is probably the most worrisome (12).

Canagliflozin was …