Diabetic ketoacidosis with dapagliflozin and carbohydrate-restricted diet

Dapagliflozin should not be administrated to patients with an increased risk for diabetic ketoacidosis, for example patients who follow a carbohydrate-restricted or ketogenic diet. However, reports from the Netherlands Pharmacovigilance Centre Lareb show that this combination is used in daily practice. 

Dapagliflozin and empagliflozin are sodium-glucose cotransporter 2 (SGLT-2) inhibitors, used in the treatment of diabetes mellitus. Lareb received four reports of diabetic ketoacidosis, three on dapagliflozin and one on empagliflozin, in which the patient also followed a carbohydrate-restricted diet. The reported indication was three times ‘type 2 diabetes’ and once ‘type 1 diabetes’. For three reports is known that the patient recovered after discontinuation of the SGLT-2 inhibitor. 

Diabetic ketoacidosis is a potential life-threatening situation that occurs when there is a lack of insulin in the body. In order to get energy, the body starts breaking down fat at a high rate. The liver processes the fat into a fuel called ketones, which causes the blood to become acidic. 

The Dutch Summary of Product Characteristics (SmPC) of dapagliflozin describes that this drug should not be administrated to patients with an increased risk for diabetic ketoacidosis. Also in literature, the association between the use of a SGLT-2 inhibitor combined with a carbohydrate-restricted diet and the occurrence of diabetic ketoacidosis has been described for patient with type 2 diabetes.