Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang
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Cox proportional hazards models estimated adjusted hazard ratios (AHRs), and sensitivity analyses addressed competing risks.</div></div><div><h3>Results</h3><div>Metformin use was linked to a lower risk of delirium (AHR, 0.86; 95% CI, 0.83–0.89) and mortality (AHR, 0.76; 95% CI, 0.74–0.78). Subgroup analyses confirmed consistent delirium risk reduction across age, sex, and glycemic control. Sensitivity analyses upheld this effect, mitigating survival bias concerns.</div></div><div><h3>Conclusions</h3><div>In this large-scale study, metformin use was associated with reduced delirium and mortality risk compared to DPP-4i, reinforcing its role as the preferred first-line T2DM therapy, especially in patients at risk for neurocognitive decline.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112270"},"PeriodicalIF":6.1000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metformin vs. second-line therapy for delirium prevention in type 2 diabetes: A multinational study\",\"authors\":\"Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang\",\"doi\":\"10.1016/j.diabres.2025.112270\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is a major risk factor for neurocognitive impairment, with delirium predicting dementia. 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Metformin vs. second-line therapy for delirium prevention in type 2 diabetes: A multinational study
Background
Type 2 diabetes mellitus (T2DM) is a major risk factor for neurocognitive impairment, with delirium predicting dementia. While metformin may offer neuroprotection, prior studies face selection bias. This study examines the association between metformin use and delirium risk compared to dipeptidyl peptidase-4 inhibitors (DPP-4i).
Methods
This multinational cohort study analyzed 860,388 T2DM patients using the TriNetX network. After propensity score matching, 84,221 metformin users were compared to 84,221 DPP-4i users. The primary outcome was delirium incidence, with secondary outcomes including all-cause mortality. Cox proportional hazards models estimated adjusted hazard ratios (AHRs), and sensitivity analyses addressed competing risks.
Results
Metformin use was linked to a lower risk of delirium (AHR, 0.86; 95% CI, 0.83–0.89) and mortality (AHR, 0.76; 95% CI, 0.74–0.78). Subgroup analyses confirmed consistent delirium risk reduction across age, sex, and glycemic control. Sensitivity analyses upheld this effect, mitigating survival bias concerns.
Conclusions
In this large-scale study, metformin use was associated with reduced delirium and mortality risk compared to DPP-4i, reinforcing its role as the preferred first-line T2DM therapy, especially in patients at risk for neurocognitive decline.
期刊介绍:
Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.