Euglycaemic ketoacidosis associated with dual-acting GLP-1/GIP receptor agonist treatment following bariatric surgery.

Abstract

Summary: Euglycaemic ketoacidosis is characterised by high anion gap metabolic acidosis with elevated serum ketone bodies in the absence of significant hyperglycaemia. Although traditionally associated with sodium-glucose cotransporter 2 (SGLT-2) inhibitors, incretin-based therapies have recently been implicated. Tirzepatide is a dual-acting glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. It is an approved treatment for obesity in patients without diabetes mellitus. We present the case of a 51-year-old woman without diabetes, 2 years after sleeve gastrectomy, who presented with nausea, vomiting and abdominal pain after rapid dose escalation of tirzepatide. Laboratory evaluation revealed severe metabolic acidosis (pH 7.01, venous bicarbonate 9.2 mmol/L), elevated serum ketones (6 mmol/L) and normal blood glucose (5 mmol/L), consistent with euglycaemic ketoacidosis. Plasma lactate was normal (1.4 mmol/L). She was managed with intravenous fluids, insulin infusion and anti-emetics until the symptoms and acidosis resolved. Tirzepatide was discontinued. This case highlights the potential for dual-acting GLP-1/GIP receptor agonists to increase susceptibility to euglycaemic ketoacidosis in patients without diabetes, particularly in the context of prior bariatric surgery. Clinicians should consider euglycaemic ketoacidosis in patients receiving dual-acting GLP-1/GIP therapy who present unwell with metabolic acidosis.

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