FAERS reports suggested GLP-1 receptor agonists differ in reported and reproductive or endocrine adverse-event signals, with semaglutide showing stronger disproportionality.
Evidence
This pharmacovigilance disproportionality analysis used FAERS Q2 2022-Q2 2025 data for six GLP-1 receptor agonists, identifying 1276 alopecia-related and 759 reproductive or endocrine-related cases and adjusted reporting odds ratios such as semaglutide alopecia aROR 1.23.
Caveat
FAERS reporting signals are vulnerable to reporting bias and confounding, so they cannot estimate true incidence or prove drug causation.
Simplified
AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database.
MATERIALS AND METHODS: This study analysed the U.S. FDA Adverse Event Reporting System (FAERS) data (Q2 2022-Q2 2025) for six GLP-1 Ras (exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide) to identify alopecia- and reproductive or endocrine-related a AEs. Disproportionality analyses were conducted using crude and adjusted reporting odds ratios (cROR and aROR) from logistic regression controlling for potential confounding factors. Sensitivity analyses with positive and negative controls were used to validate the signal robustness.
RESULTS: A total of 1276 alopecia-related and 759 reproductive or endocrine-related cases were identified. Semaglutide showed significant positive associations with alopecia (aROR 1.23 [1.11-1.35]) and reproductive/hormonal disorders, including polycystic ovary syndrome (aROR 6.59 [3.73-11.64]) and menstrual abnormalities. In contrast, dulaglutide and tirzepatide demonstrated negative associations for several reproductive outcomes (e.g., dysmenorrhoea, amenorrhoea, heavy menstrual bleeding), indicating lower reporting odds in this dataset. Sensitivity analyses using control drugs confirmed the consistency and specificity of these findings.
CONCLUSION: This real-world pharmacovigilance study identified agent-specific differences in the endocrine and dermatologic safety profiles of GLP-1 RAs. While semaglutide exhibited disproportionate reporting for alopecia and hormonal imbalance, dulaglutide and tirzepatide showed lower or non-significant disproportionality signals for these events. These results highlight the need for personalised agent selection and continued pharmacovigilance to optimise long-term patient safety.
Key numbers
1.23
Increase in Reporting Odds
Adjusted reporting odds ratio for with semaglutide.
0.37
Decrease in Erectile Dysfunction Reporting Odds
Adjusted reporting odds ratio for erectile dysfunction with dulaglutide.
6.59
Increase in PCOS Reporting Odds
Adjusted reporting odds ratio for polycystic ovary syndrome with semaglutide.
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