A Comparative Analysis of Diabetic Ketoacidosis (DKA) in Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Users Versus Non-users: A Systematic Review.

Abstract

Diabetic ketoacidosis (DKA) remains a life-threatening complication of diabetes mellitus, with emerging concerns about its association with sodium-glucose cotransporter-2 inhibitors (SGLT2i). While SGLT2i offer significant cardiovascular and renal benefits, their potential to increase DKA risk - particularly euglycemic diabetic ketoacidosis (eDKA) - warrants systematic evaluation. This review aims to compare the incidence, clinical features, and outcomes of DKA in SGLT2i users versus non-users. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, CINAHL, IEEE Xplore, and Web of Science. Eligible studies included comparative analyses of DKA in SGLT2i users and non-users, with retrospective and prospective designs. Data were extracted on incidence, laboratory features, precipitating factors, and clinical outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. Thirteen studies were included, encompassing diverse populations and regions. SGLT2i users exhibited a higher incidence of DKA, with a notable proportion presenting as eDKA. Key distinguishing features included lower blood glucose levels, higher sodium concentrations, and prolonged hospital stays. Surgery and infections were common triggers, while mortality rates remained comparable between groups. Methodological quality was generally high, though heterogeneity precluded meta-analysis. SGLT2i use is associated with an increased risk of DKA, particularly euglycemic variants, necessitating heightened clinical vigilance. Temporary discontinuation during high-risk periods and early diagnostic suspicion are recommended. Standardized criteria for eDKA and further prospective studies are needed to optimize patient safety.