Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor Related Diabetic Ketoacidosis

Abstract

Introduction: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of oral antidiabetic drugs. They can be used in some Type 2 Diabetes patients as monotherapy, in dual therapy or triple therapy or in combination with insulin. SGLT-2 inhibitors lower blood glucose by inhibiting renal reabsorption of glucose, and therefore increased urinary excretion of glucose. They are not approved for treatment of type 1 diabetes. The Medicines and Healthcare products Regulatory Agency published a warning of reports of serious and life threatening cases of diabetic ketoacidosis (DKA) in patients taking SGLT-2 inhibitors. This was followed by similar advice from the European Medicines Agency. We present a case of an elderly patient with Type 2 Diabetes Mellitus taking Empagliflozin, an SGLT-2 inhibitor, who presented with a long lie and was found to have hyperglycaemia and ketonaemia with mild acidosis. Case report: An 81-year-old gentleman was brought to A&E after spending 20 h on the floor of his house. He had earlier laid himself on the floor close to the fireplace to get warm, but was unable to get up of the floor as he had suffered a right humerus fracture two days previously. He did not eat or drink for 16 h. He denied any other symptoms. His past medical history included hypertension, type 2 diabetes, diabetic retinopathy and iron deficiency anaemia. He was on Aspirin 75 mg OD, Amlodipine 10 mg OD, Metformin 1000 mg BD, Glipizide 10 mg BD and Empagliflozin 10 mg OD. He had no known drug allergies. He was not a smoker and did not drink alcohol. He lived with his wife and was independent for activities of daily living. On examination he was dehydrated, haemodynamically stable and apart from a large reducible inguinal hernia there was no other physical findings. Urine dipstick was positive for glucose, ketones, leucocytes, blood, protein and nitrites. Capillary blood glucose was off the device's recordable scale (>33.3 mmol/L). Ketones were raised at 3.2 mmol/L. VBG showed a mild metabolic acidosis (pH 7.32). He had 10.2 9 109/L neutrophils, and blood urea was 11.6 mmol/L, otherwise FBC, kidney and liver functions and TSH were within normal. The patient was commenced on intravenous fluids, a variable rate insulin infusion, Trimethoprim for urinary tract infection, and Empagliflozin was stopped. He gradually improved and had uneventful recovery. Discussion: The use of SGLT-2 inhibitors has been linked to a small number of cases of DKA. One meta-analysis of more than 17,000 patients taking canagliflozin, a SGLT-2 inhibitor, showed a rate of DKA of 0.07%. The mechanism of SGLT-2 inhibitor related DKA is not known yet. Risk factors that may predispose patients taking SGLT-2 inhibitors to DKA include low beta cell reserve, restricted food or fluid intake, increased insulin requirements due to acute illness, surgery and alcohol abuse. In this case, the patient had a long lie on the floor without access to food or a drink and also had a urinary tract infection and a humerus fracture two days earlierFor patients on SGLT-2 inhibitors who present with acidotic symptoms, it is important to test for ketones even if plasma glucose levels are near normal. In some DKA reported cases blood glucose levels were atypically moderately elevated. SGLT-2 inhibitor should be discontinued immediately if DKA is suspected or diagnosed. Also in patients who are admitted with acute medical or surgical illness, the SGLT-2 inhibitors should be withhold till the patient is stabilised. DKA in patients taking SGLT-2 inhibitors could be life threatening.