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If diabetic ketoacidosis is suspected, the SGLT2 inhibitor should be withdrawn immediately and not restarted unless another clear precipitating factor is identified and resolved.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