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.