THU389 Euglycemic Diabetic Ketoacidosis With Prolonged Ketosis Due To SGLT-2 Inhibitor

Abstract

Abstract Disclosure: N. Viera Feliciano: None. J. Johannan: None. E. Nosova: None. C.J. Levy: Advisory Board Member; Self; Eli Lilly & Company, Dexcom. Research Investigator; Self; NIH, Helmsley Foundation, Abbott, Dexcom, Insulet, Tandem. Background: Euglycemic Diabetic ketoacidosis is a known complication of Sodium-glucose cotransporter 2 inhibitor use. Prolonged ketosis is infrequently reported on this patient population. Clinical Case: A 67-year-old male with T2DM (HbA1c 8.3%) taking dapagliflozin, metformin and semaglutide presented with emesis, polydipsia and reduced oral intake for 2 weeks. Initial tests were consistent with euglycemic diabetic ketoacidosis (eDKA): glucose 193 (70-110 mg/dL), acidosis (pH on VBG 7.27), bicarbonate 10 mmol/L (22-26 mmol/L), anion gap of 25, beta-hydroxybutyrate >4.5, positive urine ketones and glycosuria. Insulin drip was initiated along with fluid resuscitation and intravenous dextrose, followed by transition to a basal/bolus regimen after anion gap closure. Despite overall clinical improvement, the patient’s labs demonstrated persistent metabolic derangements: glycosuria and ketosis that lasted 7 days after his last dose of dapagliflozin. Implementation of an insulin regimen in this insulin-naïve patient and a carbohydrate-rich diet resulted in subsequent resolution of the derangements. The patient was discharged on metformin and insulin. eDKA is defined by a blood glucose level below 200 mg/dL, metabolic acidosis and ketosis. The cause of eDKA in this case is attributed to SGLT-2 inhibitor (SGLT2i) use, which lead to a carbohydrate deficit and depletion of glycogen stores, increased glucagon/insulin ratio resulting in ketogenesis and decreased hepatic gluconeogenesis. SGLT-2i act on proximal tubules reducing reabsorption of glucose, thereby increasing urinary glucose excretion. Dapagliflozin has an approximate half-life of 12 hours; therefore, clinical recovery from SGLT2i-associated eDKA would be expected to take up to 2-3 days after cessation of the medication. Case reports have shown persistent glucosuria and ketonemia up to 10 days after discontinuation of the drug, but the data is sparse. Our patient’s laboratory tests remained consistent with eDKA for up to 7 days, suggesting a longer lasting effect of dapagliflozin. This was managed with more aggressive insulin doses and a higher carbohydrate intake which played a critical role in correction of the insulin deficit and repletion of glycogen stores for metabolic recovery. With the growing popularity of this medication class, additional controlled studies are needed for a better understanding of the pharmacodynamics as well as how to target management strategies when eDKA occurs. In this report, we highlight the prolonged clinical effects of SGLT-2i after discontinuation and resolution of symptoms with an aggressive insulin regimen and higher carbohydrate intake. Conclusion: Use of SGLT-2i therapy for diabetes has increased the incidence of eDKA. Providers should be aware of the possibility of prolonged eDKA and manage metabolic imbalances to achieve clinical recovery in an appropriate time frame. Presentation: Thursday, June 15, 2023