Introduction
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are expected to have multifaceted effects beyond lowering blood glucose, including renoprotective effects, reduction in cardiovascular events, and reduction in hospitalizations for heart failure [1-4]. However, diabetic ketoacidosis (DKA) is a known serious adverse event of SGLT2i, and euglycemic diabetic ketoacidosis (EDKA) should receive special attention. EDKA was first reported by Munro et al. in 1973 [5], and in recent years, many EDKA cases associated with the use of SGLT2i have been reported. The Japan Diabetes Society has issued a “Recommendation on the Appropriate Use of SGLT2 Inhibitors” in Japan [6], urging caution. The Food and Drug Administration has also cautioned about the risk of DKA development with SGLT2i, and because of this risk, SGLT2i is not approved for use in type 1 diabetes mellitus (T1DM) in the United States [7].
We experienced a case of EDKA in a patient with type 2 diabetes mellitus (T2DM) on a very low-carbohydrate diet who developed EDKA only 3 days after starting SGLT2i therapy. Although the American Diabetes Association (ADA) Consensus Report indicates that low- or very-low-carbohydrate diets are an effective treatment for select patients [8], the use of SGLT2i while on a low-carbohydrate diet increases ketone production due to the lack of glucose in the body and increases the risk of ketoacidosis. Currently, SGLT2i are used not only for diabetes but also for various other diseases such as chronic kidney disease and heart failure. When initiating SGLT2i, healthcare providers should confirm the implementation of a low- or very-low-carbohydrate diet and provide intensive guidance to prevent the development of EDKA.