OR31-1 Sodium-Glucose Co-Transporter-2 Inhibitors and the Risk of Diabetic Ketoacidosis: Clinical and Biochemical Characteristics of 21 Cases

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i’s) are the newest class of anti-hyperglycemic drugs. Their mechanism of action involves increasing urinary glucose excretion by preventing glucose reabsorption in the proximal renal tubules, yet they can also promote ketogenesis under certain circumstances. Numerous reports suggest an association between SGLT2i’s and diabetic ketoacidosis (DKA), but the medical literature remains sparse. Since the use of these drugs for diabetes has increased dramatically due to favorable cardiac outcomes, identification of patients at greatest risk for this life-threatening complication is essential. Therefore, in an effort to better understand the circumstances in which SGLT2i associated DKA occurs we reviewed all available cases at our hospital over a 5-year period. Patients and Methods: We retrospectively reviewed all cases of ketoacidosis associated with SGLT2i use at our hospital from 2013 to October 2018 using an electronic medical record search algorithm. Terms included canagliflozin, dapagliflozin, empagliflozin, SGLT2 inhibitors, metabolic acidosis, ketoacidosis, diabetes, and DKA. Patients that developed DKA without being treated with SGLT2i were excluded. Results: We identified 77 cases, 21 of which met criteria for DKA associated with SGLTi use. 64% were female and 36% were male, average age was 57.8 years, BMI 29.8 kg/m(2), and mean diabetes duration was 11 years. The majority carried diagnoses of T2DM (94%) and 83.4% had no history of DKA prior to using an SGLT2i. The most common presenting symptoms were nausea, vomiting (38%), abdominal pain (28.5%) and altered mental status (19%). Common precipitants were poor oral intake (57.14%) and infection (23.8%). Average blood glucose concentrations at presentation were 329 + 36 mg/dl, interestingly, 52% of the episodes were euglycemic DKA (euDKA) with blood glucose <300 mg/dl. Average anion gap values were 25+1.4 mg/dl, bicarbonate 12.6+1.3 mg/dl and pH 7.17+0.03. All had positive urine ketones and average beta-hydroxybutyrate levels were 6.4 mmol/l. Latest hemoglobin A1c was 9.8+0.6%. A variety of drugs were prescribed along with an SGLT2i, and 62% of patients were using insulin. SGLT2i’s associated with DKA were canagliflozin (52%), empagliflozin (29%), and dapagliflozin (19%). No cases were fatal. Conclusion: We found that the majority of SGLT2i associated DKA cases occurred in older patients with type 2 DM without prior episodes of DKA. The most common presenting symptoms were nausea, vomiting, abdominal pain and altered mental status, while poor food intake and infection where the main precipitants. Clinicians should consider the possibility of ketoacidosis in SGLT2i-treated patients presenting with these symptoms, even in absence of marked hyperglycemia. If DKA is diagnosed, the SGLT2i should be discontinued and insulin therapy for DKA should be initiated.