Metformin-associated diarrhea in FAERS: a structured pharmacovigilance study with long-term temporal consistency assessment
- 1Department of Endocrinology, The Second People’s Hospital of Bengbu City , , ,
- 2Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College , , ,
Abstract
Background: Metformin-associated diarrhea is well recognized, but spontaneous-report analyses remain sensitive to outcome definition, reporting background, and incomplete event-date data. This study evaluated whether the reporting imbalance persisted across prespecified definitions, comparator sets, and calendar periods.
Methods: U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports from the first quarter of 2020 through the first quarter of 2026 were deduplicated and analyzed with metformin coded as a primary or secondary suspect drug. The primary outcome was the Medical Dictionary for Regulatory Activities preferred term DIARRHOEA. Sensitivity analyses used a broad loose-stool phenotype, a clean gastrointestinal event composite, alternative exposure roles, active comparators, co-medication exclusions, and stratification. Exact-date report-level event-date intervals among reports containing the strict-diarrhea preferred term were summarized descriptively. A separately processed dataset covering the first quarter of 2004 through the first quarter of 2026 assessed temporal consistency.
Results: Among 9,112,609 reports, 60,452 involved metformin as a primary or secondary suspect drug and 4,868 included strict diarrhea. The primary reporting odds ratio (ROR) was 2.72 (95% confidence interval, 2.64–2.80). Restriction to non-metformin antidiabetic reports attenuated the ROR to 1.95 (1.89–2.01), showing sensitivity to the reporting background. Only 595 reports (12.2%) yielded a valid report-level event-date interval; the median interval was 14 days (interquartile range, 1–363). The long-term ROR was 2.76 (2.71–2.81), with marked annual variation.
Conclusion: Metformin showed a persistent but context-dependent diarrhea reporting imbalance in FAERS. Active-comparator attenuation limits causal and clinical-risk interpretation. The selected interval subset supports descriptive reporting only and cannot define diarrhea-specific onset or a clinical monitoring window.
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BibTeX
@article{chen2026metforminassociated,
title = {{Metformin-associated diarrhea in FAERS: a structured pharmacovigilance study with long-term temporal consistency assessment}},
author = {Shida Chen and Chengan Xu},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1902348},
url = {https://europepmc.org/article/PMC/PMC13690660},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metformin-associated diarrhea in FAERS: a structured pharmacovigilance study with long-term temporal consistency assessment
AU - Shida Chen
AU - Chengan Xu
PY - 2026
DA - 2026/10/09
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1902348
UR - https://europepmc.org/article/PMC/PMC13690660
AB - Background: Metformin-associated diarrhea is well recognized, but spontaneous-report analyses remain sensitive to outcome definition, reporting background, and incomplete event-date data. This study evaluated whether the reporting imbalance persisted across prespecified definitions, comparator sets, and calendar periods. Methods: U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports from the first quarter of 2020 through the first quarter of 2026 were deduplicated and analyzed with metformin coded as a primary or secondary suspect drug. The primary outcome was the Medical Dictionary for Regulatory Activities preferred term DIARRHOEA. Sensitivity analyses used a broad loose-stool phenotype, a clean gastrointestinal event composite, alternative exposure roles, active comparators, co-medication exclusions, and stratification. Exact-date report-level event-date intervals among reports containing the strict-diarrhea preferred term were summarized descriptively. A separately processed dataset covering the first quarter of 2004 through the first quarter of 2026 assessed temporal consistency. Results: Among 9,112,609 reports, 60,452 involved metformin as a primary or secondary suspect drug and 4,868 included strict diarrhea. The primary reporting odds ratio (ROR) was 2.72 (95% confidence interval, 2.64–2.80). Restriction to non-metformin antidiabetic reports attenuated the ROR to 1.95 (1.89–2.01), showing sensitivity to the reporting background. Only 595 reports (12.2%) yielded a valid report-level event-date interval; the median interval was 14 days (interquartile range, 1–363). The long-term ROR was 2.76 (2.71–2.81), with marked annual variation. Conclusion: Metformin showed a persistent but context-dependent diarrhea reporting imbalance in FAERS. Active-comparator attenuation limits causal and clinical-risk interpretation. The selected interval subset supports descriptive reporting only and cannot define diarrhea-specific onset or a clinical monitoring window.
SN - 1663-9812
ER -