SAT-674 - Euglycemic Ketoacidosis in Non-Diabetic Patients Receiving GLP-1 Receptor Agonists for Obesity :A Case Based Systematic Review

Background

GLP-1 receptor agonists (GLP-1 RAs) are increasingly utilized for obesity management irrespective of diabetic status. Emerging case reports suggest a potential association with euglycemic ketoacidosis (EKA), a metabolic emergency characterized by ketoacidosis with near-normal glucose levels.

Methods

A systematic literature search was conducted in PubMed, Embase, and Scopus till December 2025 using combinations of terms related to GLP-1 receptor agonists (including semaglutide and tirzepatide).Eligible studies included case reports and case series involving non-diabetic adults (≥18 years) receiving GLP-1 RAs for obesity or weight management who developed euglycemic ketoacidosis, defined as blood glucose ≤200 mg/dL with metabolic acidosis (pH < 7.30 and/or bicarbonate < 18 mmol/L) and evidence of ketosis. Exclusion criteria included pre-existing diabetes, ketoacidosis from other etiologies (SGLT2 inhibitors alone, alcohol, starvation), and non-original research. Data were extracted on demographics, clinical presentation, biochemical parameters, precipitating factors, management strategies, and outcomes.

Results
A total of 129 records were identified through database searches. Following title and abstract screening, 14 articles underwent full-text screening. Of these six case reports published between 2024 and 2025 met inclusion criteria, involving exclusively female patients aged 29–48 years with body mass index ranging from 29–32 kg/m². Tirzepatide was implicated in four cases and semaglutide in two. Blood glucose at presentation ranged from 94–110 mg/dL, pH from 7.17–7.25, and serum bicarbonate from 6.2–12 mmol/L. Precipitating factors included reduced oral intake, gastrointestinal adverse effects, perioperative fasting, and medication overdose complicated by pancreatitis. All patients required hospitalization and were managed with intravenous fluids and dextrose-containing solutions; insulin therapy was generally not required. Acidosis resolved within 48–72 hours in all cases without mortality.

Conclusions
Euglycemic ketoacidosis is an emerging and potentially serious adverse event associated with GLP-1 receptor agonist use in non-diabetic patients undergoing obesity treatment. This systematic review identified six cases occurring predominantly in young to middle-aged females, frequently precipitated by reduced oral intake, gastrointestinal adverse effects, or perioperative fasting. The condition responds favorably to intravenous fluid resuscitation and dextrose administration without requiring insulin therapy. Clinicians prescribing GLP-1 RAs for weight management should counsel patients regarding adequate nutritional intake, recognize early warning signs, and maintain a high index of suspicion for this metabolic emergency, particularly during dose escalation or periods of reduced oral intake.

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