Safety Profile of Tirzepatide in Real‐World Clinical Practice: A Pharmacovigilance Study Using the FAERS Database

AIMS: Tirzepatide, a first-in-class dual GIP/GLP-1 receptor agonist, was approved by the FDA for type 2 diabetes mellitus (2022) and chronic weight management (2023). Despite superior efficacy in trials, its real-world safety profile remains incompletely characterised. This study aimed to characterise tirzepatide's post-marketing safety signals using the FAERS database. MATERIALS AND METHODS: FAERS reports listing tirzepatide as the primary suspected drug were extracted (Q2 2022-Q4 2025). Disproportionality analysis used four algorithms (ROR, PRR, IC, EBGM). Adverse events were coded using MedDRA terminology. Time-to-onset and comparative analyses versus semaglutide were conducted. RESULTS: A total of 123 145 reports (251 435 individual adverse events) were included. Females accounted for 62.30%, with a mean age of 53.7 years. Major signals included medication errors, injection-site reactions and gastrointestinal disorders. Novel unlabelled signals included eructation, hunger, food craving and starvation ketoacidosis. Compared with semaglutide, tirzepatide showed lower reporting odds of vomiting, constipation and decreased appetite. Among reports with valid onset data, median time to onset was 13 days, with 67.1% occurring within 30 days. CONCLUSIONS: This FAERS study characterises tirzepatide safety signals in real-world practice. Medication errors and injection-site reactions were the strongest signals. Several novel signals warrant further investigation. Among reports with complete onset data, most adverse events were reported early after treatment initiation, suggesting the importance of closer monitoring during the first month of therapy.