SAT-622 - Euglycemic Diabetic Ketoacidosis Associated with Semaglutide: Excessive Weight Loss and Starvation in A Frail Older Adult

Introduction

Euglycemic diabetic ketoacidosis (eDKA) is a potentially life-threatening metabolic complication that may be underrecognized due to the absence of marked hyperglycemia. Although most associated with SGLT2 inhibitors, eDKA has increasingly been reported with GLP-1 receptor agonists (GLP-1 RAs), particularly in the context of prolonged poor oral intake. Older adults may be especially vulnerable due to frailty and reduced physiologic reserves.

Clinical Case

A 91-year-old frail woman with long-standing type 2 diabetes mellitus (BMI 20.7 kg/m²) treated with metformin 1 g twice daily and oral semaglutide 14 mg daily presented with two days of vomiting after a month of dysphagia and minimal oral intake. She continued her medications until the day of admission. The patient’s diabetes was well controlled (HbA1c 6.1%) and she had lost over 30.2% of her baseline weight since the start of therapy. Laboratory evaluation demonstrated severe high–anion gap metabolic acidosis (anion gap 32 mmol/L, bicarbonate 10 mmol/L, pH 7.28) with plasma glucose of 240 mg/dL and marked ketonemia (beta-hydroxybutyrate 7.7 mmol/L), consistent with eDKA. She was also found to have acute kidney injury (creatinine 1.38 mg/dL from a baseline of 0.60 mg/dL), likely exacerbating metabolic derangements. The patient was treated with intravenous fluids with glucose and insulin infusion, with resolution of acidosis and ketosis within 48 hours. A C-peptide level of 1.5 ng/mL confirmed the presence of functioning beta cells. Islet cell autoantibodies were absent.

Conclusion
This case highlights the intersection of GLP-1 RA therapy, starvation, and frailty as contributors to eDKA in an elderly patient. The anorexigenic effects of semaglutide, combined with dysphagia and chronic reduced intake, led to a state of carbohydrate deficiency, dehydration, and relative insulin deficiency sufficient to promote ketogenesis without marked hyperglycemia. Older adults with low body mass, excessive weight loss and frailty, or declining nutritional status may be at increased risk for this complication. Clinicians should closely monitor nutritional status in elderly patients receiving GLP-1 RAs and reassess treatment goals to avoid the acute and chronic complications of excessive medication use in this vulnerable population.

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