Doctors and patients are not recognising early signs of diabetic ketoacidosis triggered by SGLT2 inhibitors, a review of 13 cases in South Australia has shown.

The life-threatening condition was often being missed due to relative euglycaemia, resulting in delayed treatment, according to a report by endocrinologist Dr Emily Mayer and colleagues at the Royal Adelaide Hospital.

Most of the cases of SGLT-2 inhibitor-related diabetic ketoacidosis (DKA) they identified from TGA adverse event reports were severe and there was one death in the period December 2015 to March 2017.

Writing in Diabetes Care, Dr Meyer and colleagues note that dapagliflozin was implicated in nine cases and empagliflozin in four cases of DKA. Nine patients required intensive care or high dependency care and all required IV insulin and dextrose.

Treating doctors overlooked the diagnosis in two cases, and in six cases they were unaware of the link between  SGLT-2 inhibitors and DKA.

Events that triggered DKA included missed insulin (5), infection (5) and surgery (3). In five cases DKA may have been triggered by reduced carbohydrate intake due to fasting for surgery or a low carb diet.

Dr Meyer and colleagues said their findings highlighted the fact that SGLT-2 inhibitor associated DKA often occurred in the absence of marked hyperglycaemia, but could be identified early through triggers and prodromic symptoms.

“Early detection of the ketotic state while symptomatic with malaise, nausea, and/or vomiting, particularly in the context of precipitants, could prompt temporary cessation of SGLT2 inhibitor, hydration, frequent carbohydrate consumption, and administration of full-dose insulin to prevent progression to DKA,” they suggested.

They also noted that DKA occurred with both type 2 diabetes (eight cases) and type 1 diabetes (five cases), with about half the patients with T2D also using insulin.

National figures showed there had been 82 reports of SGLT2 inhibitor-linked DKA in Australia up to April 2017,  most of which were serious  (mean pH 7.06, bicarbonate 7.35mmol/L, ketones 6.2mmol/L), and 16 were classified as life threatening.

Dr Meyer and colleagues said their review would help identify at-risk patients and the common precipitating factors for SGLT2 inhibitor-associated DKA.

As a precaution, they also advised temporary cessation of SGLT2 inhibitor drugs  during acute illness and surgery.

In 2015 the TGA issued an safety notice warning of the risk of DKA with SGLT 2 inhibitors.

“Early signs and symptoms of DKA include abdominal pain, nausea, vomiting, anorexia, excessive thirst, difficult breathing, unusual fatigue and sleepiness,” it said.

“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.”