Diabetic ketoacidosis with SGLT2 inhibitors

### What you need to know A 45 year old woman with type 2 diabetes complains of malaise, shortness of breath, and nausea for two days. She has been taking metformin and insulin. She was started on canagliflozin six weeks earlier to improve glycaemic control. Over the previous week she has halved the insulin dose. On examination, she is drowsy. Her respiratory rate is 28 breaths/min with a deep breathing pattern. A random blood glucose test shows 8 mmol/L (144 mg/dL). Blood tests reveal metabolic acidosis with an increased anion gap of 23 mmol/L (reference range 8-12 mmol/L), pH 7.18, and bicarbonate 14 mmol/L. Urine dipstick showed ketones +++. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, used in patients with diabetes, can cause diabetic ketoacidosis. This is rare but can be serious and life threatening. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) warn about possible “atypical” presentation of diabetic ketoacidosis with SGLT2 inhibitors12: instead of having hyperglycaemia, patients may have normal or only mildly elevated blood glucose levels (<13.9 mmol/L, <250 mg/dL). This may delay diagnosis. In 2020, the FDA and EMA updated guidance to interrupt SGLT2 inhibitors and monitor ketosis in patients scheduled for surgery or hospitalised.34 SGLT2 inhibitors, also called gliflozins, lower blood sugars by causing kidneys to remove glucose from the body in urine.5 Figure 1 depicts their actions. They are used as second or third line therapy in …