Tirzepatide is increasingly prescribed for obesity and type 2 diabetes. Although severe hypoglycaemia is uncommon in patients receiving tirzepatide who are not treated with insulin/sulfonylureas, we report a case of severe hypoglycaemia without ketosis in a non-diabetic woman prescribed tirzepatide and metformin.

A 40-year-old woman presented to the emergency department unconscious and unrousable with severe hypoglycaemia. Past medical history included polyendocrine metabolic ovarian syndrome (PMOS), iron deficiency anaemia, and alpha thalassaemia. Medications included metformin 500 mg bd and tirzepatide commenced three months prior to presentation for weight loss (weight 72 kg; BMI 28.8 kg/m2; HbA1c 5.7%). After two missed doses of tirzepatide 5mg, it was resumed two weeks prior to presentation with a dose taken three days prior to presentation. The blood glucose was initially undetectable and subsequently measured to be 1.9mmol/L (ketones 0.1mmol/L). The patient did not report a history of vomiting or prolonged fasting; weight-loss was 5 kg since commencing tirzepatide. With recurrent hypoglycaemia (2.8mmol/L), C-peptide, insulin and pro-insulin were inappropriately elevated at 3.17nmol/L, 13.9munit/L and 120.1pmol/L, respectively. Subsequent day results showed BGL 5.6mmol/L, insulin 16.0munit/L and C-peptide 1.08nmol/L. Renal, liver and thyroid function, cortisol and IGF-1 were normal with Hba1c 5.3%.

Tirzepatide and metformin were ceased. Elevated C-peptide with hypoglycaemia raised concern for insulinoma given their high GLP-1 receptor expression [1]. Elective 72-hour fast performed four-months later excluded an underlying insulinoma with nadir BGL 3.6mmol/L at 72-hours. No further episodes of hypoglycaemia had occurred.

Tirzepatide-induced hypoglycaemia is considered a possible diagnosis based on the temporal association, exclusion of alternative causes, and resolution of hypoglycaemia following tirzepatide cessation. Considering tirzepatide use continues to increase, prescribers should be aware of this potential adverse effect even in the absence of concomitant glucose lowering therapy known to be associated with hypoglycaemia.