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

Abstract

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).