The TGA has issued a safety advisory regarding odium glucose co-transporter 2 inhibitors
The TGA says it is working with sponsors of sodium glucose co-transporter 2 (SGLT2) inhibitors to update medicine information documents to strengthen warnings about the risk of diabetic ketoacidosis with these medicines.
“In particular, the risk is increased in people who undergo surgical or medical procedures,” the TGA says.
“This action has been prompted by an increase in the number of local reports received by the TGA of diabetic ketoacidosis occurring in people being treated with these medicines in Australia.”
There is a known association between treatment with SGLT2 inhibitors and diabetic ketoacidosis, information about which is available from the Product Information and Consumer Medicine Information documents for these products.
The TGA has also previously published an article about this issue in its health professional-targeted medicine safety bulletin, Medicines Safety Update, in October 2015.
It highlights early signs and symptoms of diabetic ketoacidosis, typically developed over 24 hours, including abdominal pain, nausea, vomiting, anorexia, excessive thirst, difficult breathing, unusual fatigue and sleepiness.
“The TGA continues to receive reports of diabetic ketoacidosis, including some reports of ‘euglycaemic ketoacidosis’,” it says.
Several reports involved patients who had undergone a surgical operation or a medical procedure requiring anaesthesia or light sedation, including cardiovascular, bariatric, orthopaedic or gastrointestinal procedures.
“Reports received by the TGA also included cases in which patients with type 1 diabetes had been prescribed an SGLT2 inhibitor. SGLT2 inhibitors are not registered for use in patients with type 1 diabetes.
“Risk factors in other cases included patients experiencing acute illness, such as infections, gastrointestinal conditions, cardiovascular conditions, dehydration, malnourishment/reduced caloric intake and non-adherence with insulin or reductions in insulin dose.”
As of 21 March 2018, the TGA Database of Adverse Event Notifications contains 219 reports of diabetic ketoacidosis (or metabolic acidosis) involving either empagliflozin or dapagliflozin as a suspected medicine. An increase in reporting began to emerge in mid-2017.
Fifty-seven reports have been received since December 2017 (empagliflozin 30 reports and dapagliflozin 27). Potential precipitating factors were not specified in all reports.
Of the 57 reports received since December 2017, 17 describe the use of an SGLT2 inhibitor in the period before or after a major surgical or medical procedure. There were seven reports in which patients with type 1 diabetes had been prescribed an SGLT2 inhibitor.
SGLT2 inhibitors are not registered for use in patients with type 1 diabetes. In 14 reports, an acute medical illness was described. Multiple factors predisposing to diabetic ketoacidosis were described in some cases.
Health professionals are reminded of the potential risk of diabetic ketoacidosis. Factors that predispose diabetic patients to ketoacidosis include:
- acute illness, particularly infections;
- insulin dose reduction;
- a low carbohydrate diet;
- malnourishment/reduced caloric intake;
- severe dehydration;
- previous ketoacidosis;
- insulin deficiency from any cause (such as insulin pump failure, history of pancreatitis or pancreatic surgery); and/or
- alcohol abuse.
“Treatment with an SGLT2 inhibitor should be ceased prior to major surgery,” says the TGA.
“Treatment may be restarted once the patient’s condition has stabilised following surgery and oral intake is normal. For other clinical situations known to predispose to ketoacidosis, consider monitoring for ketoacidosis and temporarily ceasing the SGLT2 inhibitor.
“You are advised to educate patients about the signs and symptoms of diabetic ketoacidosis and instruct them to immediately seek medical advice if any such symptoms are experienced.
“Patients presenting with signs and symptoms of diabetic ketoacidosis should be assessed for metabolic acidosis, even if their blood glucose levels are below 14 mmol/L, to avoid delayed diagnosis and treatment.”