{ "abstract": "Background: Neurological and neuropsychiatric complications may persist after acute kidney disease (AKD), particularly among patients with type 2 diabetes mellitus (T2DM). Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide established cardiorenal benefits, their associations with neurological outcomes after AKD remain uncertain.\n\nMethods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults with T2DM and dialysis-requiring AKD receiving GLP-1RAs or SGLT2is were identified and balanced using 1:1 propensity score matching, yielding 3,398 patients in each group. Incident delirium and other neuropsychiatric outcomes were evaluated. The 90–365-day period was the primary analysis, with 90–180- and 90–720-day windows used to assess temporal patterns. Kaplan–Meier and multivariable Cox regression analyses were performed.\n\nResults: During 90–365 days, GLP-1RA use was associated with better delirium-free survival than SGLT2i use (118/3,032 vs. 155/2,982 events; log-rank P = 0.009). This association remained significant after multivariable adjustment (adjusted hazard ratio [HR], 0.668; 95% CI, 0.488–0.914; P = 0.012). Statin use was independently associated with lower delirium risk (adjusted HR, 0.674; 95% CI, 0.492–0.924; P = 0.014), while exploratory analyses suggested a distinct association between LDL cholesterol of 100–129.9 mg/dL and delirium risk. In contrast, SGLT2i use showed a favorable association with depression during early follow-up, which attenuated over time. The GLP-1RA–delirium association was also attenuated by 90–720 days. Exploratory sensitivity analyses using non-overlapping follow-up intervals showed outcome-specific associations: adjusted differences in delirium were not significant, whereas depression and overall neurological complications were more frequent with GLP-1RA than with SGLT2i.\n\nConclusions: Among patients with dialysis-requiring AKD and T2DM, GLP-1RA and SGLT2i use showed outcome-specific associations with subsequent neuropsychiatric events. Although the primary analysis suggested a lower delirium risk with GLP-1RA, this association was not consistently observed in adjusted time-stratified analyses. These findings should be considered exploratory and require prospective validation.", "abstract_shown": true, "affiliations": [ "School of Medicine, College of Medicine, Fu Jen Catholic University", "Department of Neurology, Fu Jen Catholic University Hospital, Fu Jen Catholic University", "Department of Biology and Anatomy, National Defense Medical Center", "Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center", "Department of Health and Nutrition, Chia Nan University of Pharmacy and Science", "Department of Public Health, College of Medicine, National Cheng Kung University", "Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital", "NSARF (National Taiwan University Hospital Study Group of Acute Renal Failure) and Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKS)", "Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University", "Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University", "Department of Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei Medical University", "Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation", "School of Medicine, Tzu Chi University", "School of Post-Baccalaureate Chinese Medicine, Tzu Chi University", "Division of Nephrology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University", "Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University", "TMU Research Center of Urology and Kidney, Taipei Medical University", "Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital" ], "article_type": null, "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0, 1 ], "name": "Yu-Chen Cheng" }, { "affs": [ 2 ], "name": "Yuahn-Sieh Huang" }, { "affs": [ 3, 4, 5 ], "name": "Jui-Yi Chen" }, { "affs": [ 6, 7 ], "name": "Vin-Cent Wu" }, { "affs": [ 8, 9, 10 ], "name": "Ruei-Ming Chen" }, { "affs": [ 11 ], "name": "Kuo-Cheng Lu" }, { "affs": [ 11, 12, 13 ], "name": "Ko-Lin Kuo" }, { "affs": [ 0, 14 ], "name": "Chien-Lin Lu" }, { "affs": [ 15, 16 ], "name": "Cai-Mei Zheng" }, { "affs": [ 0, 17 ], "name": "Yi-Chou Hou" } ], "bibtex": "https://research.draconitic.com/paper/bwvyd56482w30.bib", "cited_by": 0, "doi": "10.3389/fendo.2026.1963944", "fulltext_url": null, "id": "bwvyd56482w30", "issns": [ "1664-2392" ], "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1963944/full", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2712|Diabetes Treatment and Management" ] ], "openalex": "W7224001317", "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1963944/pdf", "pmcid": null, "pmid": null, "published": "2026-10-27", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/bwvyd56482w30.ris", "sources": [ { "first_seen": "2026-10-30T12:20:20Z", "native_id": "10.3389/fendo.2026.1963944", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1963944/full" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2712|Diabetes Treatment and Management", "subfield": "endocrinology-metabolism" } ], "title": "Distinct temporal neuropsychiatric outcomes associated with GLP-1 receptor agonists versus SGLT2 inhibitors after acute kidney disease in type 2 diabetes", "title_text": "Distinct temporal neuropsychiatric outcomes associated with GLP-1 receptor agonists versus SGLT2 inhibitors after acute kidney disease in type 2 diabetes", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:20Z", "url": "https://research.draconitic.com/paper/bwvyd56482w30", "venue": "Frontiers in Endocrinology", "versions": [] }