Case Report: GADA-positive type 1 diabetes with diabetic ketoacidosis in a young adult with obesity temporally associated with unsupervised tirzepatide use for weight reduction.

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist, is widely used as an anti-obesity medication. Its safety in individuals with unrecognized type 1 diabetes (T1D) remains uncertain. Case description: We describe a 28-year-old man with obesity and no previously documented hyperglycemia who self-administered tirzepatide, lost 15 kg over about 3 months, and was later diagnosed with GADA-positive T1D presenting as diabetic ketoacidosis (DKA) in temporal association with drug use and discontinuation. At admission, fasting blood glucose (FBG) was 13.99 mmol/L, glycated hemoglobin (HbA1c) 10.8% (95 mmol/mol), serum β-hydroxybutyrate 4.44 mmol/L, urine ketones (+++), serum bicarbonate 16.9 mmol/L, glutamic acid decarboxylase antibody (GADA) >2000 IU/mL, and fasting C-peptide 0.798 ng/mL. Admission arterial blood gas was not obtained. Insulin therapy was initiated; HbA1c was 6.7% (50 mmol/mol) at 3 months. Conclusions: This single case cannot establish causality between tirzepatide exposure or discontinuation and autoimmune diabetes. It illustrates that adult-onset GADA-positive T1D with DKA may be recognized during or after unsupervised incretin-based weight reduction. Markedly elevated HbA1c indicated that hyperglycemia likely preceded the short symptomatic phase. The main clinical message is that autoimmune diabetes should be considered when unexplained hyperglycemia, ongoing weight loss, or ketoacidosis develops in this setting.