Intended for healthcare professionals

Practice Adverse Drug Reactions

Diabetic ketoacidosis with SGLT2 inhibitors

BMJ 2020; 371 doi: (Published 12 November 2020) Cite this as: BMJ 2020;371:m4147
  1. Giovanni Musso, consultant and clinical researcher1,
  2. Francesca Saba, research fellow2,
  3. Maurizio Cassader, professor3,
  4. Roberto Gambino, professor3
  1. 1Emergency and Intensive Care Medicine, HUMANITAS Gradenigo Hospital; Laboratory of Diabetology and Metabolism, Department of Medical Sciences, Città della Salute, University of Turin, Italy
  2. 2Laboratory of Diabetology and Metabolism, Department of Medical Sciences, University of Turin
  3. 3Clinical Biochemistry, Laboratory of Diabetology and Metabolism, Department of Medical Sciences, University of Turin
  1. Correspondence to: G Musso giovanni_musso{at}

What you need to know

  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors are relatively new drugs approved for diabetes, but they increase the risk for diabetic ketoacidosis, particularly in patients with type 1 diabetes and those with certain high risk conditions

  • In some cases blood glucose levels are normal or only mildly elevated, a condition known as euglycaemic ketoacidosis, which can delay the diagnosis

  • Check ketones in patients taking SGLT2 inhibitors with symptoms or precipitating factors for ketoacidosis regardless of blood glucose levels

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

What are SGLT2 inhibitors?

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 …

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