Hou Zhong-Bao, Chou Yu-Ching, Yang Tsan, Sun Chien-An
Department of Public Health, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
School of Public Health, National Defense Medical Center, Taipei City 11490, Taiwan.
Healthcare (Basel). 2025 Jun 27;13(13):1537. doi: 10.3390/healthcare13131537.
: Diabetes is rapidly increasing in developing and industrializing nations, primarily due to type 2 diabetes (T2DM). With the global prevalence of diabetes steadily increasing, estimates suggest that by 2045, nearly 548 million people will be living with the disease worldwide. Alzheimer's disease (AD), recognized as the primary contributor to dementia in aging populations, exhibits an escalating prevalence that parallels the demographic shifts toward older age groups worldwide. This progressive neurodegenerative disorder has emerged as a critical public health challenge, with epidemiological patterns closely tracking the trajectory of population aging across industrialized and developing nations. This study investigates whether metformin may help reduce the risk of dementia. Previous studies from various countries have explored the association between metformin use and dementia risk; however, the findings have been inconsistent. Therefore, we conducted this study to examine whether the observed protective effect of metformin also applies to the Taiwanese (Han Chinese) population, potentially providing valuable insights into ethnic or regional differences in drug response. : We conducted a retrospective cohort study using data from the Longitudinal Health Insurance Database 2000 (LHID2000), including 2 million individuals from 2000 to 2013. Patients with T2DM aged ≥40 years who initiated metformin between 2000 and 2005 formed the exposed group, while those starting other second-line antidiabetic medications formed the non-exposed group. Propensity score matching was used to control for age, sex, index date, and major comorbidities. Incident dementia (2007-2013) was identified using relevant ICD-9-CM codes. Adjusted hazard ratios were estimated using Cox regression with time-dependent covariates. : The metformin-exposed cohort demonstrated a risk reduction for dementia incidence relative to the comparator group (adjusted HR 0.472, 95% CI = 0.328-0.679). This protective association remained robust in sex-stratified analyses and age-stratified subgroups. Temporal analysis further revealed a duration-dependent risk attenuation, with extended therapeutic exposure correlating with progressive dementia risk decrement. : Our findings suggest that metformin use may be associated with a lower risk of developing dementia in individuals with type 2 diabetes mellitus.
糖尿病在发展中国家和工业化国家中正在迅速增加，主要原因是2型糖尿病（T2DM）。随着全球糖尿病患病率稳步上升，据估计到2045年，全球将有近5.48亿人患有这种疾病。阿尔茨海默病（AD）被认为是老年人群痴呆症的主要病因，其患病率不断上升，与全球人口向老年群体的转变趋势一致。这种进行性神经退行性疾病已成为一项严峻的公共卫生挑战，其流行病学模式在工业化国家和发展中国家紧密追踪着人口老龄化的轨迹。本研究调查二甲双胍是否有助于降低痴呆症风险。来自不同国家的先前研究探讨了二甲双胍使用与痴呆症风险之间的关联；然而，研究结果并不一致。因此，我们开展了这项研究，以检验观察到的二甲双胍的保护作用是否也适用于台湾（汉族）人群，这可能为药物反应的种族或地区差异提供有价值的见解。
我们使用2000年纵向健康保险数据库（LHID2000）的数据进行了一项回顾性队列研究，该数据库包含2000年至2013年的200万个人。2000年至2005年间开始使用二甲双胍的年龄≥40岁的T2DM患者组成暴露组，而开始使用其他二线抗糖尿病药物的患者组成非暴露组。倾向评分匹配用于控制年龄、性别、索引日期和主要合并症。使用相关的ICD-9-CM编码识别2007年至2013年的新发痴呆症。使用具有时间依赖性协变量的Cox回归估计调整后的风险比。
与对照组相比，二甲双胍暴露队列的痴呆症发病率风险降低（调整后的HR为0.472，95%CI = 0.328 - 0.679）。这种保护关联在按性别分层分析和按年龄分层的亚组中仍然很强。时间分析进一步揭示了一种与持续时间相关的风险衰减，治疗暴露时间延长与痴呆症风险逐渐降低相关。
我们的研究结果表明，使用二甲双胍可能与2型糖尿病患者患痴呆症的风险较低有关。
