{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:48:42Z","timestamp":1785786522404,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>This study examined the association between metformin\u2010based oral antihyperglycemic combination therapy and the risk of developing dementia in patients with newly diagnosed type 2 diabetes mellitus (T2DM).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We conducted a retrospective cohort study using data from a random sample of 2,000,000 individuals in Taiwan's National Health Insurance Research Database from 2000 to 2018. A total of 44,073 patients with newly diagnosed T2DM were identified and categorized into four groups based on initial treatment: metformin (MET)\u2010sulfonylureas (SU), MET\u2013dipeptidyl peptidase\u20104 inhibitor (DPP4i), MET\u2013thiazolidinedione (TZD), and MET\u2013glinides. The participants were followed until December 2018.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The hazard ratio of MET\u2013TZD was 0.73 (95% confidence interval [CI]: 0.57\u20130.94), of MET\u2013DPP4i was 0.64 (95% CI: 0.52\u20130.79), and of MET\u2013glinides was 1.14 (95% CI: 0.94\u20131.39).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>The MET\u2013DPP4i group had the lowest risk of dementia, followed by the MET\u2013TZD group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Newly diagnosed type 2 diabetes mellitus (T2DM) patients using metformin (MET)\u2013glinides and MET\u2013sulfonylureas are at an increased risk of dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The MET\u2013glinides group had the highest risk of dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The MET\u2013dipeptidyl peptidase\u20104 inhibitor group had the lowest risk of dementia, followed by the MET\u2013thiazolidinedione group.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70590","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T02:55:08Z","timestamp":1755485708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metformin\u2010based oral antihyperglycemic combination therapy and risk of dementia in patients with newly diagnosed type 2 diabetes: A population\u2010based study"],"prefix":"10.1002","volume":"21","author":[{"given":"Tsung\u2010Cheng","family":"Hsieh","sequence":"first","affiliation":[{"name":"Institute of Medical Sciences Tzu Chi University  Hualien City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang\u2010Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health Tzu Chi University  Hualien City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Chuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Consulting Center Department of Medical Research Buddhist Tzu Chi Medical Foundation Hualien Tzu Chi Hospital  Hualien City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5580-7846","authenticated-orcid":false,"given":"Chen\u2010Pei","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Buddhist Tzu Chi Medical Foundation Hualien Tzu Chi Hospital  Hualien City Taiwan"},{"name":"Department of Nursing College of Nursing Tzu Chi University Hualien City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"World Alzheimer Report 2023","author":"ADI","year":"2023"},{"key":"e_1_2_9_3_1","volume-title":"Understanding Dementia","author":"TADA"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2014.05.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01911-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004867420972763"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2013.845086"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-201535"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu073"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100944"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087095"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.07.004"},{"issue":"2","key":"e_1_2_9_13_1","first-page":"86","article-title":"Diabetes mellitus and dementia: a literature review","volume":"29","author":"Lin Y","year":"2018","journal-title":"J Intern Med"},{"issue":"3","key":"e_1_2_9_14_1","first-page":"249","article-title":"[National guidelines for the prevention and control of diabetes in primary care (2022)]","volume":"61","author":"Chinese Diabetes Society; National Office for Primary Diabetes Care","year":"2022","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S331948"},{"key":"e_1_2_9_16_1","unstructured":"DAROC Clinical Practice Guidelines for Type 2 Diabetes Care\u20142022. 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