{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:40:29Z","timestamp":1790905229575,"version":"4.1.0"},"reference-count":23,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"publisher","award":["2025-0033"],"award-info":[{"award-number":["2025-0033"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,2,9]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5\u20132 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer\u2019s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Multicentre, retrospective, observational, new-user, active-comparator cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study analysed 24\u2009172 matched pairs for stroke outcomes (40\u2009483 person-years in the SGLT2 inhibitor group and 39\u2009363 person-years in the TZD group), 25\u2009111 matched pairs for dementia (41\u2009924 person-years in the SGLT2 inhibitor group and 40\u2009726 person-years in the TZD group) and 25\u2009237 matched pairs for AD (42\u2009139 person-years in the SGLT2 inhibitor group and 40\u2009895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95%\u2009CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95%\u2009CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95%\u2009CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-105271","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T18:35:22Z","timestamp":1771785322000},"page":"e105271","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative risk of the neurodegenerative outcomes between sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones in type 2 diabetes: a multicentre cohort study using the Korean healthcare database (2014\u20132025)"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-6115","authenticated-orcid":false,"given":"Sang Joon","family":"Park","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihae","family":"Seo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Won","family":"Byun","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoil","family":"Suh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Hi","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"},{"name":"Elim Thyroid Clinic, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inho","family":"Lee","sequence":"additional","affiliation":[{"name":"Informatization Project Department, Soonchunhyang University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Hyo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-7397","authenticated-orcid":false,"given":"Minjae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Soonchunhyang University Hospital Seoul, Yongsan-gu, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Oh","family":"Mok","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soon Chun Hyang University Hospital Bucheon, Bucheon-si, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-2062","authenticated-orcid":false,"given":"Dae-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan-si, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Young","family":"Sohn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Goyang-si, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4989-3287","authenticated-orcid":false,"given":"Rae Woong","family":"Park","sequence":"additional","affiliation":[{"name":"Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Woo","family":"Seo","sequence":"additional","affiliation":[{"name":"Internal Medicine, Kangdong Sacred Heart Hospital, Gangdong-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-6612","authenticated-orcid":false,"given":"So Yoon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Daegu Catholic University Hospital, Daegu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Youl","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Dongdaemun-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon-Myoung","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Sejong General Hospital, Bucheon-si, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Myung","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic 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Dementia in Europe Yearbook 2019: Estimating the Prevalence of Dementia in Europe. 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Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis. 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