Incidence of ketoacidosis in diabetic patients treated with sodium–glucose cotransporter-2 inhibitors: A prospective cohort study

Introduction: Sodium–glucose cotransporter 2 inhibitors (SGLT2is) have gained significant attention for their benefits in managing type 2 diabetes mellitus (T2DM), particularly in patients with chronic kidney disease (CKD) and heart failure. However, the potential for SGLT2is to increase the risk of ketoacidosis, particularly euglycemic diabetic ketoacidosis (EDKA), warrants further investigation. This prospective cohort study assesses the incidence of ketoacidosis among T2DM patients treated with SGLT2is and examines related risk factors. Methods: This is a prospective study included 575 patients with T2DM. Patients over 18 years undergoing SGLT2i therapy were followed for six months. Baseline demographics, clinical history, glucose management practices, and medication use, with an emphasis on SGLT2is, were recorded. Blood gas analysis (BGA) and urine ketones were measured monthly. Ketoacidosis was defined by urine ketone positivity with pH <7.30, bicarbonate (HCO3) ≤18 mEq/L, and an elevated anion gap. Results: Out of 575 patients, 35.6% (205) had positive urine ketones at least once during the study, with 11 patients (0.7%) meeting ketoacidosis criteria. Patients with ketoacidosis had a mean hospital stay of 8.2 days compared to 5.4 days in non-ketoacidosis patients (p = 0.02). No in-hospital mortality occurred among ketoacidosis patients. Conclusion: Ketoacidosis was rare but clinically relevant in T2DM patients on SGLT2is. The incidence of euglycemic ketoacidosis highlights the need for monitoring and identifying high-risk individuals early during SGLT2i treatment initiation.