Last year, FDA was warning that treatment with SGLT2 inhibitors may lead to ketoacidosis based on the search of the FDA Adverse Event Reporting System database which have identified 20 cases of diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT2 inhibitors· The SGLT2 inhibitor-induced ketoacidosis is characterized by relatively low glucose level (euglycemic DKA) compared to typical DKA· It is pathophysiologically plausible that SGLT2 inhibition induces ketogenesis and predisposes to the development of ketoacidosis· SGLT2 inhibitor-induced glycosuria reduces insulin secretion· In contrast, glucagon concentrations increase significantly partly because of a diminished paracrine inhibition of insulin and possibly also because of decreased SGLT2-mediated glucose transport into α-cells· Moreover, whole body metabolism shifts happen; shortage of glucose increases lipolysis and fatty acid oxidation· Thus ketogenesis is increased· In actual clinical studies of tofogliflozin and ipragliflozin, dose dependent and significant increase of plasma ketone body levels was reported· However, all of the ketogenesis does not develop to ketoacidosis· The estimated incidence rates are 0·5 and 0·8 per 1000 patient-years with canagliflozin 100mg and canagliflozin 300mg· In case of dapagliflozin and empagliflozin, the frequency of reported events could estimate less than 0·1%· Euglycemic DKA induced by SGLT2 inhibitors can be predictable and manageable· Both of physician and patients have to be aware of the risks and symptoms of ketoacidosis· If the patients who have been treated with SGLT2 inhibitor experience malaise, nausea, vomiting, or shortness of breath especially after alcohol intake, insulin dose reduction or during inter-current illness, they have to stop the SGLT2 inhibitor use, to take a large amount of fluid and carbohydrates and to visit hospital·