MON-656 - Euglycemic Diabetic Ketoacidosis Following GLP-1 Receptor Agonist Dose Escalation in A Patient on SGLT2 Inhibitor Therapy

Introduction
Euglycemic diabetic ketoacidosis (euDKA) is a known complication associated with sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) dose escalation is an underrecognized precipitating factor for euDKA in patients already on SGLT2 inhibitors.

Case
A 41-year-old woman with type 2 diabetes mellitus, hypertension, hyperthyroidism, and hyperlipidemia presented to the Emergency Department with nausea, vomiting, abdominal pain and body aches for 24 hours. These symptoms began one day after an increase in semaglutide from 1 mg to 2 mg injectable weekly. She had decreased oral intake due to the nausea and vomiting episodes following semaglutide dose increase. She continued to take empagliflozin 25 mg daily for her diabetes management. However, she was non-adherent with her basal insulin at home. On arrival, the patient was tachycardic with a heart rate of 129 beats per minute and hypertensive (203/125 mmHg). Physical exam was notable for dry oral mucosa. Laboratory evaluation showed high anion gap metabolic acidosis (bicarbonate 17 mmol/L, anion gap 21, venous pH 7.312), serum glucose 249 mg/dL, lactate 2.9 mmol/L, positive serum ketones, and urine ketones >80 mg/dL with glucosuria. The hemoglobin A1c was 11.9%. Imaging and infectious workup were unremarkable. The patient was admitted to the intensive care unit for euDKA attributed to the decreased oral intake and dehydration from recent GLP-1 RA dose escalation in the context of ongoing SGLT2 inhibitor therapy. She was managed with intravenous insulin infusion, dextrose containing fluids and electrolyte repletion. The anion gap closed, bicarbonate improved, acidosis resolved, and she was transitioned to subcutaneous insulin. She tolerated oral intake and was discharged on basal insulin. A two-week clinic follow-up confirmed that she was doing well on the new regimen.

Conclusion
This case underscores the potential for GLP-1 RA dose escalation to trigger euDKA in patients already on SGLT2 inhibitors, particularly in the context of insulin deficiency and reduced caloric intake. Sick day management, including temporarily discontinuing SGLT2 inhibitors during illness, may be essential when increasing GLP-1 RA doses in patients on both medications.

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