A Literature Review of the Therapeutic Perspectives of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor-Induced Euglycemic Diabetic Ketoacidosis

Abstract

Euglycemic diabetic ketoacidosis (DKA), a side effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors, is a triad of high metabolic anion gap acidosis, raised serum and urine ketones, and serum glucose <250 mg/dl. SGLT2 inhibitors cause a carbohydrate deficit by glucosuria, which leads to an increased glucagon/insulin ratio, the metabolic shift from glucose to lipid utilization causing ketogenesis, and hence euglycemic DKA. Additional factors like the ketogenic diet, illness, surgery, and pregnancy contribute to precipitating these episodes. Keywords search included "Euglycemic DKA and SGLT2 inhibitors" in PubMed and Google Scholar, to compile data from existing articles that provide information on the withholding and restarting period of the drug after a euglycemic DKA episode. SGLT2 inhibitors, used in the treatment of type 2 DM, have an average half-life of 11-13 hours, so most articles suggested withholding the drug three days before any elective surgery but some articles suggested a longer withholding period based on other precipitating factors contributing to euglycemic DKA. Hence, we came up with patient inclusion criteria and concomitant therapies review that we need to consider in making this decision. In addition, a multidisciplinary approach is required when laying out guidelines for restarting the drug to have a unanimous approach. After reviewing the existing literature, it is clear that concrete guidelines are required to decide on drug withholding and restarting periods after a euglycemic DKA episode, as they vary among different institutions and different specialties. We believe it is crucial to consider patient inclusion criteria and concomitant therapies in forming those guidelines.