Metformin vs. second-line therapy for delirium prevention in type 2 diabetes: A multinational study

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-05-20 DOI:10.1016/j.diabres.2025.112270

Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang

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Abstract

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.

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二甲双胍与二线治疗预防2型糖尿病谵妄：一项多国研究。

背景：2型糖尿病（T2DM）是神经认知功能障碍的主要危险因素，谵妄可预测痴呆。虽然二甲双胍可能提供神经保护，但先前的研究面临选择偏差。本研究考察了与二肽基肽酶-4抑制剂（DPP-4i）相比，二甲双胍使用与谵妄风险之间的关系。方法：这项跨国队列研究使用TriNetX网络分析了860,388例T2DM患者。在倾向评分匹配后，84221名二甲双胍使用者与84221名DPP-4i使用者进行了比较。主要结局是谵妄发生率，次要结局包括全因死亡率。Cox比例风险模型估计调整后的风险比（AHRs），敏感性分析处理竞争风险。结果：二甲双胍的使用与谵妄的风险降低有关(AHR, 0.86；95% CI, 0.83-0.89)和死亡率(AHR, 0.76；95% ci, 0.74-0.78)。亚组分析证实，在不同年龄、性别和血糖控制情况下，谵妄风险降低一致。敏感性分析支持这种效应，减轻了生存偏差的担忧。结论：在这项大规模的研究中，与DPP-4i相比，二甲双胍的使用与谵妄和死亡风险的降低有关，加强了其作为首选的一线T2DM治疗的作用，特别是在有神经认知能力下降风险的患者中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

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.