{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T20:09:53Z","timestamp":1774901393728,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["CRC\u20102020\u201000353"],"award-info":[{"award-number":["CRC\u20102020\u201000353"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Residents of Ontario, Canada \u226566 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population\u2010based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%\u20138.0% and estimated glomerular filtration rate \u226545\u00a0mL\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup> were selected. Using the landmark method to address immortal time bias, exposure was grouped into \u201cmetformin monotherapy initiation within 180 days after new diabetes diagnosis\u201d or \u201cno glucose\u2010lowering medications within 180 days.\u201d To address disease latency, 1\u2010year lag time was applied to the end of the 180\u2010day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity\u2010score weighted Cox proportional hazard models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over mean follow\u2010up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (<jats:italic>N<\/jats:italic>\u00a0=\u00a012,331; 978 events; 65,762 person\u2010years) showed no association with dementia risk (aHR [95% CI]\u00a0=\u00a01.05 [0.96\u20131.15]), compared to delayed or no glucose\u2010lowering medication initiation (<jats:italic>N<\/jats:italic>\u00a0=\u00a022,369; 1768 events; 117,415 person\u2010years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13723","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T15:49:41Z","timestamp":1695656981000},"page":"68-78","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes"],"prefix":"10.1111","volume":"295","author":[{"given":"Che\u2010Yuan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Sandra Black Centre for Brain Resilience and Recovery Hurvitz Brain Sciences Program Sunnybrook Research Institute  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christa","family":"Wang","sequence":"additional","affiliation":[{"name":"ICES  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