Sodium glucose co-transporter 2 inhibitors - used to treat type 2 diabetes

Safety advisory - risk of diabetic ketoacidosis

13 August 2015

Consumers and health professionals are advised that serious cases of diabetic ketoacidosis (DKA) have been reported in patients taking prescription medicines that are inhibitors of sodium glucose co-transporter 2 (SGLT2).

These medicines include canagliflozin, dapagliflozin or empagliflozin, which are used to help lower blood sugar levels in patients with type 2 diabetes.

Early signs and symptoms of DKA include abdominal pain, nausea, vomiting, anorexia, excessive thirst, difficult breathing, unusual fatigue and sleepiness. If DKA is not diagnosed early and treatment initiated, more serious signs and symptoms including dehydration, deep gasping breathing, confusion and coma can potentially develop.

DKA occurs most commonly in patients with type 1 diabetes, although it can occur in type 2 diabetes. It is usually accompanied by high blood glucose levels.

However, in a number of the cases of DKA associated with SGLT2 inhibitors, patients demonstrated only a moderately increased blood glucose level. This could lead to delayed diagnosis and treatment.

Affected brands include:

  • Invokana (canagliflozin) tablets – 100 mg and 300 mg
  • Forxiga (dapagliflozin) tablets – 10 mg
  • Xigduo XR (dapagliflozin and metformin hydrochloride XR) tablets – 5 mg/1000 mg, 10 mg/1000 mg and 10 mg/500 mg
  • Jardiance (empagliflozin) tablets – 10 mg and 25 mg.

The sponsors of these medicines have jointly written to health professionals to provide further information about this issue, including recommendations for patient management.

Information for consumers

The above information relates to a potential risk associated with these medicines.

If you or someone you care for takes one of the affected products, you should continue taking your medicine until advised otherwise by your health professional.

However, if you experience abdominal pain, nausea, vomiting, anorexia, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness, you should immediately seek medical advice.

If you have any questions or concerns about this issue, speak to your diabetes nurse educator or other health professional.

Information for health professionals

Health professionals are advised that in reported cases of the above issue, the presentation of DKA was sometimes atypical. While DKA typically occurs at glucose levels greater than 14 mmol/L (250 mg/dL), glucose levels in some cases were only mildly elevated at less than 11 mmol/L (200 mg/dL).

You should inform patients of signs and symptoms of metabolic acidosis (such as, nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness) and advise them to immediately seek medical advice if they develop any such signs or symptoms.

Patients being treated with SGLT2 inhibitors should be assessed for DKA when they present with signs or symptoms of metabolic acidosis in order to prevent delayed diagnosis and patient management.

If DKA is suspected, treatment with SGLT2 inhibitors should be discontinued. 

If DKA is confirmed, appropriate measures should be taken to correct the DKA and to monitor glucose levels.

In some of the reported cases, just before or at the same time as the DKA occurred, patients experienced acute illness (such as, urinary tract infection, urosepsis, gastroenteritis, influenza, trauma or surgery), reduced caloric or fluid intake, and/or reduced insulin dose. The underlying mechanism for SGLT2 inhibitor-associated DKA has not been established.

Some of the reported cases involved off-label use in patients with type 1 diabetes. Prescribers are reminded that SGLT2 inhibitors should be used according to their respective Product Information. Type 1 diabetes is not an approved indication for these medicines.

If you have any further questions or concerns about this issue, you can contact the relevant sponsor using the below details:

Reporting problems

Consumers and health professionals are encouraged to report problems with medicines or vaccines. Your report will contribute to the TGA's monitoring of these products.

The TGA cannot give advice about an individual's medical condition. You are strongly encouraged to talk with a health professional if you are concerned about a possible adverse event associated with a medicine or vaccine.