SGLT2 inhibitors, including canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, are licensed for use in adults with diabetes to improve glycaemic control. Diabetic ketoacidosis, a serious complication of diabetes caused by low insulin levels, is a rare adverse effect of these drugs.
2016 safety review
The risk of diabetic ketoacidosis associated with SGLT2 inhibitors was confirmed in 2016 following a European review of the evidence. Prescribers were subsequently advised to notify patients of the risks and to counsel them on risk factors and actions to take if they developed signs or symptoms of ketoacidosis.
In addition, the product information for all SGLT2 inhibitors was updated to include a recommendation to interrupt therapy in patients admitted to hospital for major surgery or acute serious illness and to not restart treatment until the patient's condition has stabilised.
In 2019 a new European review was conducted to assess reports of peri-operative ketoacidosis in patients being treated with SGLT2 inhibitors. The review recommended that the warnings for these drugs be updated to include routine monitoring of ketones in patients hospitalised for surgery or acute illness, an approach which aims to help identify patients who are at risk (or in the early stages) of ketoacidosis so that prompt corrective measures can be applied.
Monitor blood ketones
The review recommends testing for ketones in blood rather than urine, on the basis that SGLT2 inhibitors may diminish the excretion of ketone bodies in the urine, thereby making urine testing less reliable than blood testing.
The review was not able to identify any particular type of surgery as being linked to an increased risk of peri-operative ketoacidosis nor was it able to make specific recommendations relating to peri-operative management such as a specific time-point to stop or restart SGLT2 inhibitors or management of food intake and insulin use.