Plain Language Summary
Updated FAERS pharmacovigilance analysis of tirzepatide adverse events (Q1 2022–Q1 2025) using Python/MySQL data processing with an adapted time-to-onset method, systematically characterizing emerging safety signals as tirzepatide prescribing expanded from initial approval through the obesity indication. Identifies new and updated adverse event signals with temporal onset characterization. Provides the most current comprehensive tirzepatide pharmacovigilance assessment—capturing three years of post-marketing safety data with time-to-onset analysis that enables prescribers to anticipate when adverse events are most likely to occur during therapy.
Abstract
PURPOSE: Tirzepatide, the first dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist with rapidly expanding clinical use, requires detailed post-marketing pharmacovigilance to monitor emerging safety signals. This study aims to identify and characterize specific adverse events (AEs) associated with tirzepatide utilizing FDA Adverse Event Reporting System (FAERS).
PATIENTS AND METHODS: The datasets were cleaned and standardized using Python, a programming language for data processing, and MySQL, a database management system, to ensure accuracy and consistency before analysis. Subsequently, AE signals were detected via four quantitative disproportionality algorithms, sorted and categorized by demographics, gender, and clinical prioritization, with a modified Weibull model developed to analyze AE onset timing.
RESULTS: A total of 67,305 cases (75.83% female) and 137,583 adverse events were identified related to tirzepatide. One hundred and forty-four AE signals showed statistically significant signals suggesting a potential association with tirzepatide, with several new including postmenopausal haemorrhage and menstrual disorder (implying regulatory interference on sex hormones), Wernicke's encephalopathy and sleep disorder (malnutrition caused by low intake). Pancreatitis, impaired gastric emptying, dehydration and cholelithiasis carried higher risks with serious clinical outcomes. Sleep disorder, delayed gastric emptying, and medullary thyroid cancer are more common in males; starvation ketoacidosis and incorrect injection site, in females. The median time-to-onset (TTO) was 6.36 days (Interquartile Range (IQR) 0.85-31.2) with the Weibull shape parameter (β) of 0.44, indicating an early failure profile.
CONCLUSION: This study uncovered new risks of tirzepatide, including AEs associated with skin, menstruation, psychiatric and nervous system. Median TTO was corrected to within a week, highlighting the need for early monitoring before clinicians prescribe tirzepatide, and special attention should be given to patients who have pre-existing digestive dysfunction, malnutrition, or a family history of thyroid disease.