Severe diabetic ketoacidosis associated with insulin dose reduction after tirzepatide initiation

A man in his 50s with insulin-treated type 2 diabetes mellitus presented with a 1-day history of severe abdominal pain, nausea and vomiting, 15 days after initiation of tirzepatide. On admission, he was severely dehydrated with profound high-anion gap metabolic acidosis (pH 6.8), marked hyperglycaemia and ketosis, consistent with severe diabetic ketoacidosis (DKA), requiring intensive therapy unit admission. He had been treated with insulin for over 10 years, with preserved renal function (estimated glomerular filtration rate 80 mL/min/1.73 m²), haemoglobin A1c of 61 mmol/mol and no previous history of DKA. Tirzepatide 2.5 mg once a week was commenced, and a telephone review 6 days after the first dose confirmed mild bloating with preserved oral intake and continued insulin use. Following the second dose, gastrointestinal symptoms progressed, resulting in complete inability to tolerate food or fluids for 24 hours prior to admission. During this period, the patient reduced his basal insulin glargine dose from 40 to 20 units for 3 days due to fear of hypoglycaemia. This case highlights the importance of reinforcing sick-day rules and continuation of basal insulin when initiating tirzepatide in insulin-treated patients.