BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a 
class of antihyperglycemic agents that increase urinary glucose excretion by 
interfering with the reabsorption of glucose in the proximal renal tubules. In 
May of 2015, the U.S. Food and Drug Administration released a warning concerning 
a potential increased risk of ketoacidosis and ketosis in patients taking these 
medications.
CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes 
mellitus taking a combination of canagliflozin and metformin who presented with 
progressive altered mental status over the previous 2 days. Her work-up 
demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH 
of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 
500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated 
serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She 
was treated with intravenous insulin and fluids, and the metabolic abnormalities 
and her altered mental status resolved within 36 h. This was the first episode 
of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY 
PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications 
are at risk for ketoacidosis. Due to the renal glucose-wasting properties of 
these drugs, they may present with ketoacidosis with only mild elevations in 
serum glucose, potentially complicating the diagnosis. Acetone is one of the 
three main ketone bodies formed during DKA and it may be present at considerable 
concentrations, contributing to the serum osmolality.