Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
William Doran, Louis Tunnicliffe, Rutendo Muzambi, Christopher T Rentsch, Krishnan Bhaskaran, Liam Smeeth, Carol Brayne, Dylan M Williams, Nish Chaturvedi, Sophie V Eastwood, Susanna J Dunachie, Rohini Mathur, Charlotte Warren-Gash
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引用次数: 0

Abstract

Introduction 4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence is conflicting. We therefore aimed to assess the association between metformin therapy and risk of incident all-cause dementia or MCI compared with other oral glucose-lowering therapies (GLTs). Research design and methods We conducted an observational cohort study using the Clinical Practice Research Datalink among UK adults diagnosed with diabetes at ≥40 years between 1990 and 2019. We used an active comparator new user design to compare risks of dementia and MCI among individuals initially prescribed metformin versus an alternative oral GLT using Cox proportional hazards regression controlling for sociodemographic, lifestyle and clinical confounders. We assessed for interaction by age and sex. Sensitivity analyses included an as-treated analysis to mitigate potential exposure misclassification. Results We included 211 396 individuals (median age 63 years; 42.8% female), of whom 179 333 (84.8%) initiated on metformin therapy. Over median follow-up of 5.4 years, metformin use was associated with a lower risk of dementia (adjusted HR (aHR) 0.86 (95% CI 0.79 to 0.94)) and MCI (aHR 0.92 (95% CI 0.86 to 0.99)). Metformin users aged under 80 years had a lower dementia risk (aHR 0.77 (95% CI 0.68 to 0.85)), which was not observed for those aged ≥80 years (aHR 0.95 (95% CI 0.87 to 1.05)). There was no interaction with sex. The as-treated analysis showed a reduced effect size compared with the main analysis (aHR 0.90 (95% CI 0.83 to 0.98)). Conclusions Metformin use was associated with lower risks of incident dementia and MCI compared with alternative GLT among UK adults with diabetes. While our findings are consistent with a neuroprotective effect of metformin against dementia, further research is needed to reduce risks of confounding by indication and assess causality. Data may be obtained from a third party and are not publicly available. The data used for this study were obtained from the CPRD. Access to CPRD data is subject to protocol approval via CPRD’s Research Data Governance Process (see ). Data acquisition is associated with a fee and data protection requirements. Code lists used to define health conditions in this study have been made openly available on LSHTM Data Compass: ().
接受二甲双胍与其他口服降糖药治疗的 2 型糖尿病患者的痴呆症发病风险:利用英国初级医疗保健记录开展的一项观察性队列研究
导言:英国有 420 万人患有 2 型糖尿病,这是痴呆症和轻度认知障碍 (MCI) 的已知风险因素。糖尿病治疗可能会改变这种关联,但现有证据并不一致。因此,我们旨在评估二甲双胍治疗与其他口服降糖药物 (GLT) 相比,与全因痴呆或 MCI 发病风险之间的关联。研究设计与方法 我们利用临床实践研究数据链对 1990 年至 2019 年间确诊糖尿病的年龄≥40 岁的英国成年人进行了一项观察性队列研究。我们采用主动比较者新用户设计,在控制社会人口学、生活方式和临床混杂因素的情况下,使用 Cox 比例危险度回归法比较了最初处方二甲双胍与替代口服 GLT 的患者患痴呆症和 MCI 的风险。我们评估了年龄和性别的交互作用。敏感性分析包括治疗分析,以减少潜在的暴露误分类。结果 我们纳入了 211 396 人(中位年龄为 63 岁;42.8% 为女性),其中 179 333 人(84.8%)开始接受二甲双胍治疗。在中位 5.4 年的随访中,服用二甲双胍可降低痴呆症(调整 HR (aHR) 0.86 (95% CI 0.79 至 0.94))和 MCI(调整 HR 0.92 (95% CI 0.86 至 0.99))的风险。80岁以下二甲双胍使用者的痴呆风险较低(aHR 0.77 (95% CI 0.68 to 0.85)),而年龄≥80岁者的痴呆风险则较低(aHR 0.95 (95% CI 0.87 to 1.05))。与性别没有交互作用。与主要分析(aHR 0.90 (95% CI 0.83 to 0.98))相比,治疗分析显示效应大小有所降低。结论 在英国成年糖尿病患者中,与替代 GLT 相比,使用二甲双胍与较低的痴呆症和 MCI 发病风险相关。虽然我们的研究结果与二甲双胍对痴呆症的神经保护作用一致,但仍需进一步研究,以减少适应症混淆的风险并评估因果关系。数据可能来自第三方,不对外公开。本研究使用的数据来自 CPRD。访问 CPRD 数据需通过 CPRD 的研究数据管理流程(见)进行方案审批。数据获取需要支付一定的费用,并有数据保护要求。本研究中用于定义健康状况的代码表已在 LSHTM Data Compass 上公开发布:()。
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来源期刊
BMJ Open Diabetes Research & Care
BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
9.30
自引率
2.40%
发文量
123
审稿时长
18 weeks
期刊介绍: BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.
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