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

summaryEuglycaemic 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. LEARNING POINTS: