Dietary Changes Leading to Euglycemic Diabetic Ketoacidosis in Sodium-Glucose Cotransporter-2 Inhibitor Users: A Challenge for Primary Care Physicians?

Abstract

Background: The use of euglycemic diabetic ketoacidosis (EDKA) related to sodium-glucose cotransporter 2 inhibitors (SGLT2i) use in people with diabetes has been increasingly reported. The causes are multifactorial, and dietary changes in SGLT2i users were observed to trigger EDKA. A ketogenic diet or very low-carbohydrate diet (VLCD) enhances body ketosis by breaking down fats into energy sources, causing EDKA. This study aimed to understand the patient specific risk factors and clinical characteristics of this cohort.Methods: Several databases were carefully analyzed to understand the patients’ symptoms, clinical profile, laboratory results, and safety of dietary changes in SGLT2i’s. Thirteen case reports identifying 14 patients on a ketogenic diet and SGLT2i’s diagnosed with EDKA were reviewed.Results: Of the 14 patients, 12 (85%) presented with type-2 diabetes mellitus (DM) and 2 (15%) presented with type-1 DM. The duration of treatment with SGLT2i before the onset of EDKA varies from 1 to 365 days. The duration of consuming a ketogenic diet or VLCD before EDKA onset varies from 1 to 90 days, with over 90% of patients hospitalized <4 weeks after starting the diet. At presentation, average blood glucose was 167.50±41.80 mg/dL, pH 7.10±0.10, HCO₃ 8.1±3.0 mmol/L, potassium 4.2±1.1 mEq/L, anion-gap 23.6±3.5 mmol/L, and the average hemoglobin A1c was 10%±2.4%. The length of hospital stay ranged from 1 to 15 days. None of the patients were reinitiated on SGLT2i’s, and 50% (2/4) of the patients reported were on the ketogenic diet or VLCD upon patient questioning.Conclusion: Despite the popularity of the ketogenic diet and VLCD for weight loss, their use in diabetics taking SGLT2i’s is associated with EDKA. Physicians should educate patients with diabetes taking SGLT2i’s about the risk of EDKA. In addition, patients should be encouraged to include their physicians in any decision related to significant changes in diet or exercise routines. Further research is needed to address if SGLT2i’s should be permanently discontinued in patients with diabetes on SGLT2i and whether the ketogenic diet developed EDKA.