Comparative Gynecological Safety of the Dual GIP/GLP-1 Receptor Agonist Tirzepatide vs. the GLP-1 Receptor Agonist Semaglutide: A Real-World Pharmacovigilance Analysis (2022–2025)

TL;DR

This study compares the gynecological safety of tirzepatide and semaglutide using real-world data and finds no significant difference in hemorrhagic event reports.

Contribution

The study provides new real-world pharmacovigilance evidence on the comparative gynecological safety of dual GIP/GLP-1 and GLP-1 therapies.

Findings

Gynecological hemorrhage rates were 0.60% for tirzepatide and 0.62% for semaglutide.

The reporting odds ratio (ROR) was 0.97, indicating no statistically significant difference.

Consumer-driven reporting was significantly higher for tirzepatide (94.6%) compared to semaglutide (53.4%).

Abstract

Background

The rapid adoption of incretin-based therapies for obesity has raised questions regarding their comparative safety profiles. While the gynecological safety of glucagon-like peptide-1 (GLP-1) receptor agonists is documented, the potential risks associated with dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonism remain less characterized. This study aimed to evaluate the reporting patterns of gynecological hemorrhagic events associated with tirzepatide compared to semaglutide using real-world pharmacovigilance data.

Methods

A retrospective disproportionality analysis was conducted of the FDA Adverse Event Reporting System (FAERS) database from Q1 2022 to Q3 2025. Cases of gynecological hemorrhage were identified using standardized MedDRA queries. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated to compare the reporting frequency of hemorrhagic events between tirzepatide and semaglutide.

Results

A total of 103,607 female-specific reports were analyzed (tirzepatide: n = 70,768; semaglutide: n = 32,839). Gynecological hemorrhagic events were reported in 0.60% of tirzepatide cases and 0.62% of semaglutide cases. The ROR for tirzepatide versus semaglutide was 0.97 (95% CI = 0.82-1.14), indicating no statistically significant difference in reporting odds. A significant disparity in reporter sources was observed, with 94.6% of tirzepatide reports originating from consumers compared to 53.4% for semaglutide.

Conclusions

This analysis of post-marketing surveillance data did not detect a disproportionate reporting signal suggesting an increased risk of gynecological hemorrhagic events with tirzepatide compared to semaglutide. While these findings suggest a comparable safety profile, the high proportion of consumer-driven reporting for tirzepatide warrants cautious interpretation. Future prospective studies are needed to confirm these findings in controlled clinical settings.