Sodium-glucose cotransporter-2 inhibitors induced eu-glycemic diabetic ketoacidosis: The first report in a type 2 diabetic (T2D) Taiwanese and literature review of possible pathophysiology and contributing factors

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the newest class of oral antidiabetic drugs (OADs), approved to be a second-line OAD for type 2 diabetes in Taiwan since 2016. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had both released statements associating the use of SGLT-2 inhibitors may increase the risk of eu-glycemic diabetic ketoacidosis (euDKA). This review reveals the possible pathophysiology with a chain of metabolic adaptions to decrease plasma glucose and increase plasma ketone bodies through pancreas, kidney, liver and adipose tissue. Moreover, euDKA is a potential and rare complication of treatment with SGLT-2 inhibitors when coexisting with triggering factors. It is an emerging challenge for clinical physicians and patients treated with SGLT-2 inhibitors. Therefore, first report of SGLT-2 inhibitor induced euDKA in a T2D Taiwanese and literature review of possible pathophysiology and contributing factors are presented in order to make more attentions in public. Keywords: Sodium-glucose cotransporter-2 inhibitors, Eu-glycemic diabetic ketoacidosis, Ketosis, Type 2 diabete