Empagliflozin/insulin

Abstract

Euglycaemic diabetic ketoacidosis and hypophosphataemia: case report A 71-year-old man developed euglycaemic diabetic ketoacidosis (DKA) and hypophosphataemia during treatment with empagliflozin and insulin, respectively. The man was admitted to the intensive care ward because of qualitative impaired consciousness, tachypnoea and tachycardia with arterial hypotension with suspected sepsis. According to his wife, cerebellar syndrome with intention tremor and ataxia, pronounced proximal paresis on the left and cognitive impairment, which was present with known fragile X-associated tremor ataxia syndrome (FXTAS), had worsened in the previous few days. In the days before admission, he had also increasingly eaten and drunk less. He was treated with a suprapubic bladder catheter because of autonomic dysfunction and benign prostatic hyperplasia. He was diagnosed with type 2 diabetes mellitus in 2010. Therefore, the overweight patient received a combination preparation with metformin and sitagliptin and applied a Glucagon-likepeptide-1 (GLP-1) receptor agonist. Oral empagliflozin 25 mg/day had been added to the antidiabetic therapy approximately 6 months before the hospitalisation. The neurological examination showed a somnolent, dysarthric patient with rest tremor. Breathing was accelerated and deepened. He was tachycardic and hypotonic but normothermic. Clinical signs of exsiccosis were present, but no evidence of an infection focus was noted. Urine tests showed evidence of a nitrite-positive urinary tract infection, glucosuria and ketonuria. Laboratory chemistry revealed acute kidney damage, hyperglycaemia and only minimally elevated inflammation parameters. In the blood gas analysis, a pronounced metabolic acidosis with a pH of 7.0, a standard bicarbonate of 3.0 mmol/l and excess anion gap (∆AG) of 36 mmol/L was observed. A diagnosis of euglycaemic DKA secondary to empagliflozin use was considered. The man was admitted to the ICU, and empagliflozin was withdrawn. To suppress ketogenesis, a combined therapy with insulin and glucose intake was administered. In the process, a continuous administration of up to 12 IU/h insulin (via perfusor) was necessary because of the only moderately elevated blood glucose values, and concomitant administration of glucose application in order to successively suppress the ketogenesis, to compensate for the metabolic acidosis and to normalise the activated ∆AG. Potassium was substituted early on insulin administration, sodium bicarbonate administration was not necessary. In spite of early phosphate supplementation (already 8h after the start of insulin therapy), he developed hypophosphataemia up to 0.2 mmol/L, which however remained clinically inapparent. After 48 hours, he could be transferred to the general ward. In view of the metabolic imbalance, the glutamate decarboxylase antibodies were determined to rule out latent autoimmune diabetes in adulthood (latent autoimmune diabetes in adults [LADA]). Treatment of type 2 diabetes was continued on an outpatient basis with a combination preparation of metformin and sitagliptin as well as intensified insulin therapy after recovery of renal function there and over the further course.