SUN-653 - SGLT2 Inhibitor-Associated Euglycemic DKA Represents A Distinct Metabolic and Management Phenotype: A Real-World Cohort Study

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are increasingly associated with euglycemic diabetic ketoacidosis (euDKA); however, real-world clinical characteristics, management patterns, and metabolic outcomes remain poorly characterized.

Methods: We conducted a retrospective cohort study of adults hospitalized between 2019 and 2023 with ICD-10 codes for diabetic ketoacidosis (DKA) or anion gap metabolic acidosis. Among 22,545 screened admissions, 98 cases with documented SGLT2i use were identified, and 63 with confirmed recent exposure (during admission or discontinued ≤1 week prior) were verified by manual chart review. DKA was defined by metabolic acidosis (pH ≤7.30 or bicarbonate ≤18 mmol/L) and ketosis (β-hydroxybutyrate ≥3.0 mmol/L and/or moderate urine ketones). Patients were categorized into three groups: euDKA (n=16; glucose ≤250 mg/dL), hyperglycemic DKA (hyperDKA; n=14; glucose >250 mg/dL), and non-DKA (n=33; including hyperosmolar hyperglycemic state or ketosis not meeting DKA criteria). Categorical variables were compared using chi-square or Fisher’s exact tests, and continuous variables using parametric or nonparametric tests.

Results: Among patients with euDKA, the most common precipitants were reduced carbohydrate intake or starvation (18.8%), pancreatic disease (18.8%), and infection (18.8%), followed by GLP-1 receptor agonist–associated gastrointestinal intolerance (12.5%) and postoperative stress (12.5%). Ischemic heart disease differed significantly among groups and was most prevalent in the non-DKA group (euDKA: 12.5%; hyperDKA: 35.7%; non-DKA: 51.5%; p=0.030). Renal function also differed, with greatest impairment in hyperDKA, reflected by higher serum creatinine (1.16±0.48 vs. 2.01±1.54 vs. 1.57±1.12 mg/dL) and lower estimated glomerular filtration rate (67.9±20.7 vs. 46.5±22.2 vs. 58.4±21.9 mL/min/1.73m²; p≤0.011). Despite lower admission glucose levels, management and metabolic outcomes differed. euDKA patients were less likely to receive standardized DKA order sets (87.5% vs. 100% vs. 63.6%; p=0.013) or initial NPO orders (50.0% vs. 92.9% vs. 77.4%; p=0.023). IV insulin infusion duration differed among groups (45.3±35.8 vs. 60.5±43.6 vs. 39.8±32.1 hours; p=0.005). Time to bicarbonate normalization was longer in euDKA compared with non-DKA, with intermediate values in hyperDKA (46.7±38.9 vs. 41.2±37.7 vs. 32.9±29.6 hours; p=0.039).

Conclusions: SGLT2i-associated euDKA represents a distinct metabolic and management phenotype that is under-recognized. Despite lower glycemic burden at presentation, euDKA patients experienced delayed metabolic resolution and less frequent use of standardized DKA protocols, highlighting the need for improved recognition and management strategies.

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