Healthcare professionals should be aware of possible atypical cases

The European Medicines Agency (EMA) has confirmed recommendations to minimise the risk of diabetic ketoacidosis in patients taking SGLT2 inhibitors (a class of type 2 diabetes medicines).

Diabetic ketoacidosis is a serious complication of diabetes caused by low insulin levels. Rare cases of this condition, including life-threatening ones, have occurred in patients taking SGLT2 inhibitors for type 2 diabetes and a number of these cases have been atypical, with patients not having blood sugar levels as high as expected.

An atypical presentation of diabetic ketoacidosis can delay diagnosis and treatment. Healthcare professionals should therefore consider the possibility of ketoacidosis in patients taking SGLT2 inhibitors who have symptoms consistent with the condition even if blood sugar levels are not high.

Following a review of the cases, EMA has recommended updating the product information of SGLT2 inhibitors to list diabetic ketoacidosis as a rare adverse reaction (affecting up to 1 in 1,000 patients).

Patients taking these medicines should be aware of the symptoms of diabetic ketoacidosis, including rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat. Patients should contact a doctor or the nearest hospital straightaway if they have any of these symptoms.

If diabetic ketoacidosis is suspected or confirmed, treatment with SGLT2 inhibitors should be stopped immediately and should not be re-started unless another cause for the ketoacidosis is identified and resolved.

Healthcare professionals should exercise caution with SGLT2 inhibitors in patients with risk factors for ketoacidosis and inform patients of these factors. These include low insulin-producing capacity in the pancreas, a sudden drop in a patient’s insulin dose, increased insulin requirement (due to illness, surgery or alcohol abuse) or conditions that can restrict food intake or lead to severe dehydration.

In addition, EMA recommends temporarily stopping SGLT2 inhibitors in patients who are undergoing major surgery or are in hospital due to serious illness.

Finally, EMA reminds healthcare professionals that SGLT2 inhibitors are not authorised for type 1 diabetes, noting that cases of ketoacidosis have also occurred during off-label use and clinical trials in type 1 diabetes.

The benefits of these medicines continue to outweigh the risks in the treatment of type 2 diabetes.

EMA’s recommendations are based on an initial review by its Pharmacovigilance Risk Assessment Committee (PRAC). The recommendations were then sent to theCommittee for Medicinal Products for Human Use (CHMP), which has now confirmed them and issued the Agency’s final opinion.

The CHMP’s opinion will now be sent to the European Commission for a legally-binding decision valid throughout the EU.

Posted on the EMA website on 26 February 2016