Analysis of nearly 38,000 FDA adverse event reports for tirzepatide found GI issues dominate in men while injection site reactions are more common in women, with starvation ketoacidosis flagged as an unexpected risk.
37,827 reportsFDA adverse event analysis of tirzepatide identified 100 significant safety signals including unexpected starvation ketoacidosis, with side effects appearing at a median of 23 days
What the researchers found
Analysis of 37,827 adverse event reports for tirzepatide in the FDA's FAERS database identified 100 statistically significant adverse event signals. The most commonly reported events were incorrect dose administered, injection site pain, off-label use, nausea, and injection site hemorrhage. An unexpected safety signal — starvation ketoacidosis — was identified.
Notably, side effects differed between sexes: men primarily reported gastrointestinal disorders, while women more commonly reported general disorders and injection site reactions. The median time to onset for adverse events was 23 days after starting tirzepatide.
Why it matters
With millions of people now using tirzepatide (Mounjaro/Zepbound), real-world safety data from spontaneous reporting systems like FAERS captures adverse events that clinical trials — which are controlled and time-limited — may miss. The identification of starvation ketoacidosis as an unexpected signal is clinically important, and the sex-based differences in side effect patterns could inform personalized monitoring strategies.
The numbers in context
37,827 ADE reports · 100 significant signals · Top 5: incorrect dose, injection site pain, off-label use, nausea, injection site hemorrhage · Median onset: 23 days · Starvation ketoacidosis: unexpected signal · Sex-specific patterns identified
How the study worked
Pharmacovigilance study mining the FDA Adverse Event Reporting System (FAERS) database from Q2 2022 through Q1 2024. Disproportionality analyses used four validated algorithms (ROR, PRR, BCPNN, MGPS) to identify statistically significant adverse event signals. Only events flagged by all four algorithms were considered significant. Sex-specific subgroup analyses were performed.
Who was studied
37,827 adverse event reports associated with tirzepatide in the FDA FAERS database from Q2 2022 to Q1 2024
What this study cannot tell us
FAERS is a spontaneous reporting system subject to reporting bias — serious events are overreported while mild events are underreported. Reports don't prove causation; many patients have comorbidities and take other medications. Off-label use as a 'top 5 event' reflects reporting patterns rather than a true adverse event. The database cannot calculate true incidence rates (no denominator of total users). Duplicate reports may inflate numbers.
How to read the evidence
FAERS pharmacovigilance studies provide important real-world safety signals but cannot establish causation or calculate true incidence rates. The use of four independent disproportionality algorithms strengthens the signal detection, but FAERS data is subject to reporting bias.
When this study was published
Published in 2024 using FAERS data from 2022–2024. This captures the earliest real-world safety experience with tirzepatide and will be supplemented by larger datasets as use continues.
The bigger picture
As GLP-1 drugs become some of the most prescribed medications worldwide, post-market safety surveillance becomes critical. Clinical trials tested tirzepatide in thousands of carefully selected patients, but real-world use involves millions of diverse individuals — including those with conditions that would have excluded them from trials. The starvation ketoacidosis signal is particularly relevant because it may occur in patients who dramatically reduce food intake on the drug, a known behavioral pattern with GLP-1 agonists.
Questions still open
- Is starvation ketoacidosis occurring in patients who drastically reduce caloric intake on tirzepatide, and should dietary counseling be strengthened?
- Why do side effect patterns differ between men and women — is this related to hormonal differences, injection technique, or body composition?
- How do tirzepatide's real-world adverse event patterns compare to semaglutide's FAERS profile?
Common questions
What is starvation ketoacidosis and why was it flagged?
Do men and women experience different side effects on tirzepatide?
Read the original research
Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.
Frontiers in pharmacology, 15, 1463657
Citation
Ou, Yingyong; Cui, Zhiwei; Lou, Siyu; Zhu, Chengyu; Chen, Junyou; Zhou, Linmei; Zhao, Ruizhen; Wang, Li; Zou, Fan. (2024). Analysis of tirzepatide in the US FDA adverse event reporting system (FAERS): a focus on overall patient population and sex-specific subgroups.. Frontiers in pharmacology, 15, 1463657. https://doi.org/10.3389/fphar.2024.1463657