Exploring Hypoglycemic Ketoacidosis in Nondiabetic Patients on Tirzepatide: Is Starvation the Culprit?

BACKGROUND Tirzepatide is a long-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist administered via subcutaneous injection for weight reduction and treating type 2 diabetes. CASE REPORT We report case series of hypoglycemic ketoacidosis after the use of tirzepatide to treat nondiabetic patients with obesity from Kuwait. The first case was a 29-year-old woman with a body mass index (BMI) of 32 kg/m² who developed abdominal pain and vomiting after increasing the dose to 5 mg subcutaneously in week 5 of treatment. The second case was a 34-year-old woman with a BMI of 31.3 kg/m² who presented with abdominal pain, vomiting, and diarrhea after increasing the dose to 5 mg subcutaneously. The third case was a 17-year-old girl with a BMI of 30.4 kg/m2 who presented with abdominal pain, vomiting, and diarrhea in week 5 of treatment. The fourth case was a 26-year-old woman with a BMI of 30.8 kg/m² who presented with abdominal pain, frequent loose motions, and vomiting. The median blood sugar level was <3.89 mmol/L and high anion gap metabolic acidosis with ketosis occurred. All the patients required inpatient treatment with intravenous fluid and the correction of hypoglycemia and ketosis. CONCLUSIONS Tirzepatide can induce hypoglycemic ketoacidosis in nondiabetic patients with obesity when used for weight reduction. Measuring urine and serum ketone levels in patients with gastrointestinal symptoms who are taking dual GLP-1 and GIP receptor agonists is crucial. Medical supervision is recommended when this medication is prescribed.