{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T21:10:08Z","timestamp":1778101808355,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J R Soc Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors may exert neuroprotective effects. However, the comparative efficacy of individual agents remains unclear. This network meta-analysis (NMA) aimed to evaluate the differential impacts of these therapies on the incidence of mental status changes, specifically delirium, depression, dementia and coma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A frequentist NMA was conducted using data from randomised controlled trials (RCTs) investigating GLP-1 receptor agonists or SGLT2 inhibitors. The robustness of the findings was verified through a Bayesian NMA framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting:<\/jats:title>\n                    <jats:p>This study adopted a confirmatory framework focusing on pre-defined neuropsychiatric adverse outcomes in alignment with Cochrane recommendations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants:<\/jats:title>\n                    <jats:p>Included trials enrolled individuals without baseline cognitive or psychiatric disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures:<\/jats:title>\n                    <jats:p>The primary endpoint was the incidence of delirium, depression, dementia or coma during treatment. Secondary endpoints included changes in cognitive performance and drop-out rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A total of 62 RCTs comprising 200,068 participants were included. Among all treatments, only high-dose dapagliflozin (10\u2009mg\/day) significantly reduced the occurrence of delirium and depression, particularly in patients with type 2 diabetes. Dulaglutide and liraglutide were the only agents associated with cognitive improvement. No significant benefits were observed for dementia or coma across all agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This analysis highlights agent-specific neuroprotective profiles: SGLT2 inhibitors, especially high-dose dapagliflozin, may mitigate the onset of delirium and depression, while GLP-1 receptor agonists, notably dulaglutide and liraglutide, may enhance cognitive function. These findings warrant consideration in selecting antihyperglycemic therapies for individuals at elevated neuropsychiatric risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>PROSPERO CRD42024601021.<\/jats:p>\n                    <jats:p>The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB E202516007).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/01410768251395877","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T17:21:54Z","timestamp":1765214514000},"page":"46-54","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression, dementia and coma: evidence from a network meta-analysis"],"prefix":"10.1177","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-7800","authenticated-orcid":false,"given":"Ping-Tao","family":"Tseng","sequence":"first","affiliation":[{"name":"Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan"},{"name":"Prospect Clinic for Otorhinolaryngology &amp; Neurology, Kaohsiung 811, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing-Yan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan"},{"name":"Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-4060","authenticated-orcid":false,"given":"Chih-Wei","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mein-Woei","family":"Suen","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan"},{"name":"Gender Equality Education and Research Center, Asia University, Taichung 413, Taiwan"},{"name":"Department of Medical Research, Asia University Hospital, Asia University, Taichung 413, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Ming","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan"},{"name":"School of Medicine, College of Medicine, I-Shou University, Kaohsiung 840, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre F.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3220, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendon","family":"Stubbs","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London WC2R 2LS, UK"},{"name":"Department of Sport, University of Vienna, Vienna 1010, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Prospect Clinic for Otorhinolaryngology &amp; 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