{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T14:21:54Z","timestamp":1768573314947,"version":"3.49.0"},"posted":{"date-parts":[[2025,11,27]]},"group-title":"Epidemiology","reference-count":9,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To systematically identify potential safety signals associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with type 2 diabetes (T2D) using a high-throughput target trial emulation pipeline applied to real-world data.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We utilized electronic health record (EHR) data from the OneFlorida+ Data Trust (2012\u20132023). Using a retrospective new-user cohort design, we compared SGLT2i initiators to initiators of other second-line glucose-lowering drugs (GLDs). We evaluated risk across all ICD-10-CM 4-digit diagnosis codes. A semi-Bayesian shrinkage method was employed to adjust hazard ratios (HR) and p-values to account for multiple testing and stabilize estimates for rare outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The analysis identified several statistically significant safety signals. Validating our method, we observed known adverse events such as candidiasis of the vulva and vagina (HR=1.64) and other urogenital fungal infections. We also detected potential signals for conditions such as viral conjunctivitis and melanocytic nevi.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This high-throughput screening effectively identified both known and potential new safety signals for SGLT2i. The use of semi-Bayesian shrinkage provides a robust framework for post-marketing surveillance in large healthcare databases.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.25.25341015","type":"posted-content","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T22:10:18Z","timestamp":1764281418000},"source":"Crossref","is-referenced-by-count":0,"title":["High-Throughput Safety Signal Detection for Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-3759","authenticated-orcid":false,"given":"Hao","family":"Dai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao An","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-5429","authenticated-orcid":false,"given":"Jiang","family":"Bian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025112818301408000_2025.11.25.25341015v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1600827"},{"key":"2025112818301408000_2025.11.25.25341015v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0099-6"},{"key":"2025112818301408000_2025.11.25.25341015v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708282114"},{"key":"2025112818301408000_2025.11.25.25341015v1.4","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S009"},{"key":"2025112818301408000_2025.11.25.25341015v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6607"},{"key":"2025112818301408000_2025.11.25.25341015v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"issue":"1","key":"2025112818301408000_2025.11.25.25341015v1.7","first-page":"195","article-title":"Bayesian perspectives for epidemiological research","volume":"36","year":"2007","journal-title":"II. Regression analysis. Int J Epidemiol"},{"issue":"7","key":"2025112818301408000_2025.11.25.25341015v1.8","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1111\/dom.16385","article-title":"A review of the safety of sodium-glucose co-transporter-2 inhibitors","volume":"27","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"2025112818301408000_2025.11.25.25341015v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2017.10.008"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.11.25.25341015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:52:11Z","timestamp":1768510331000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.11.25.25341015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":9,"URL":"https:\/\/doi.org\/10.1101\/2025.11.25.25341015","relation":{},"subject":[],"published":{"date-parts":[[2025,11,27]]},"subtype":"preprint"}}