SAT-610 - Euglycemic Diabetic Ketoacidosis after GLP-1 Receptor Agonist Initiation in A Patient Receiving Chronic SGLT2 Inhibitor Therapy

Background

Sodium-glucose cotransporter -2 (SGLT2) inhibitors are associated with an increased risk of euglycemic diabetic ketoacidosis (euDKA). In contrast, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are not classically associated with diabetic ketoacidosis. As combined SGLT2 inhibitors and GLP-1RAs are becoming increasingly common, understanding rare but serious adverse interactions is essential. We report a case of severe euDKA occurring shortly after initiation of Tirezepatide in a patient with long-term SGLT inhibitor use.

Case Presentation:

A 48-year-old man with poorly controlled type 2 diabetes mellitus presented with fatigue and dyspnea. He had been treated with empagliflozin and metformin for approximately two years without prior episodes of ketoacidosis. One week prior to the presentation, tirzepatide was initiated.

Initial laboratory evaluation revealed glucose 239 mg/dL, bicarbonate 7 mmol/L, anion gap 24, venous PH 6.97, and markedly elevated serum acetone at 11.22 mmol/L, Hemoglobin A1c 11.1%.

Diabetes-associated autoantibodies were negative, consistent with severe euglycemic DKA. No infectious or other precipitating etiology was identified. The patient was managed with intravenous insulin and intravenous fluids in the intensive care unit. Following closure of anion gap, he was transitioned to subcutaneous insulin. Empagliflozin and Tirezepatide were discontinued, and he was discharged on insulin therapy with endocrinology follow up.


Conclusion:

This case demonstrates that initiation of GLP-1 receptor agonist may precipitate euglycemic diabetic ketoacidosis (euDKA ) in patients receiving chronic SGLT2 inhibitor therapy, particularly in the setting of poor baseline glycemic control. Although GLP-1 RAs are not independently associated with diabetic ketoacidosis, their effects on appetite suppression, reduced caloric intake, and relative insulin deficiency may potentiate SGLT2 inhibitor-mediated ketogenesis, thereby increasing euDKA risk. Clinicians should maintain heightened awareness of euDKA risk when initiating GLP-RAs in patients on SGLT2 inhibitors and emphasize symptom recognition and sick-day management.

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