{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:31Z","timestamp":1791521431976,"version":"4.3.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u20132.80). Restriction to non-metformin antidiabetic reports attenuated the ROR to 1.95 (1.89\u20132.01), 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\u2013363). The long-term ROR was 2.76 (2.71\u20132.81), with marked annual variation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1902348","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:27:24Z","timestamp":1791520044000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin-associated diarrhea in FAERS: a structured pharmacovigilance study with long-term temporal consistency assessment"],"prefix":"10.3389","volume":"17","author":[{"given":"Shida","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The Second People\u2019s Hospital of Bengbu City","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S183","DOI":"10.2337\/dc26-S009","article-title":"9. 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