Commentary: In May 2015, the FDA announced a potential association between SGLT-2 inhibitors and high anion gap metabolic acidosis accompanied by elevation in urine or serum ketones.¹ It emphasized that the reported cases were not associated with the high glucose levels usually seen in diabetic ketoacidosis and that clinicians should think of ketoacidosis in patients presenting with symptoms consistent with ketoacidosis, including tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, and mental status changes even when tested blood glucose levels were not in the range usually seen with ketoacidosis. The frequency of this presentation is not clear. The study reviewed above of more than 17,000 patients suggests that this condition is relatively rare, with an incidence in the study group similar to the usual diabetic population. Nonetheless, this new entity of diabetic ketoacidosis with relatively non-elevated glucose levels is important for clinicians to be aware of in appropriate patients on SGLT-2 inhibitors. —Neil Skolnik, MD

1. FDA website. FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm Update May 15, 2015. Accessed August 7, 2015.