New advice on diabetic ketoacidosis risk with SGLT2 inhibitors

Measures to reduce the risk of rare diabetic ketoacidosis in patients taking SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) have been updated following a review by the European Medicines Agency.

The SGLT2 inhibitors dapagliflozin, canagliflozin and empagliflozin are available as single agents and in combination with metformin.
The SGLT2 inhibitors dapagliflozin, canagliflozin and empagliflozin are available as single agents and in combination with metformin.

The risk of diabetic ketoacidosis in patients taking SGLT2 inhibitors was highlighted in 2015 following reports of rare but serious cases of the complication. New precautions have now been announced in a letter to healthcare professionals from the manufacturers of the drugs. 

A number of the reports involved off-label use of SGLT2 inhibitors in patients with type I diabetes, which is not an approved indication for this class of drugs.

Risk factors

Further information
View SGLT2 inhibitor drug records
Summaries of Product Characteristics
Letter to healthcare professionals
MIMS Diabetes Clinic

Before starting treatment with dapagliflozin (Forxiga, Xigduo), canagliflozin (Invokana, Vokanamet) or empagliflozin (Jardiance, Synjardy), the following predisposing factors for diabetic ketoacidosis should be considered and caution used if any are present:

  • low beta-cell function reserve (eg, low C-peptide levels, latent autoimmune disease in adults, or a history of pancreatitis)
  • restricted food intake or severe dehydration
  • sudden reduction in insulin
  • increased insulin requirements due to acute illness
  • surgery
  • alcohol abuse.

Atypical presentation

Patients taking SGLT2 inhibitors should be advised to report symptoms of diabetic ketoacidosis (nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness), and diagnosis should be considered if these occur. Blood glucose levels may not be significantly increased as is usual in patients with diabetic ketoacidosis, prescribers are warned.

If diabetic ketoacidosis is suspected, the SGLT2 inhibitor should be withdrawn immediately and not restarted unless another clear precipitating factor is identified and resolved.

Treatment with an SGLT2 inhibitor should also be interrupted if a patient is hospitalised for a major procedure or an acute serious medical illness.

Prescribers are urged to continue reporting suspected side-effects of SGLT2 inhibitors via the Yellow Card scheme.

NICE guidance

The new quick-reference MIMS summary of the recently updated NICE clinical guidance on type II diabetes covers NICE's advice on the place of SGLT2 inhibitors in the treatment pathway. 

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