Global Health Management and Policy, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Section of Endocrinology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
BMJ Open. 2019 Jul 30;9(7):e024954. doi: 10.1136/bmjopen-2018-024954.
This study aimed to evaluate the association between metformin treatment and the risk of neurodegenerative disease (ND) among elderly adults with type 2 diabetes mellitus (T2DM).
DESIGN/SETTING/PARTICIPANTS: This retrospective longitudinal cohort study examined the effects of the length of metformin exposure on ND among elderly US veterans with T2DM and insulin treatment using the Veterans Affairs electronic medical record database.
The primary clinical outcome was defined as diagnosis of ND including dementia, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and mild cognitive impairment during the follow-up period. The secondary clinical outcomes were separately measured by AD, PD, HD, dementia and mild cognitive impairment.
Adjusted by propensity score weight, a total of 5528 patients (mean age, 63.2±10.9 years; male, 98%; white, 60%) with a median follow-up of 5.2 years were selected. Those with ND or other mental disorders at baseline or who were on insulin for less than two-thirds of the study period were excluded. The incidence rate of ND was 11.48 per 1000 person-years among patients with metformin treatment, compared with 25.45 per 1000 person-years for those without metformin. Compared with no metformin use, 2-4 years and >4 years of metformin exposure were significantly associated with lower risk of ND (adjusted HR (aHR)=0.62, 95% CI 0.45 to 0.85; aHR=0.19, 95% CI 0.12 to 0.31, respectively), while metformin exposure in the first 2 years showed no significant influence.
We conclude that long-term metformin therapy (>2 years) was associated with lower incidence of ND among elderly veterans with T2DM. We need to conduct a study with more representative population and more robust method for causal inferences. Further investigation into the mechanism involved is needed along with randomised trials to confirm a potential neuroprotective effect of metformin.
本研究旨在评估二甲双胍治疗与老年 2 型糖尿病（T2DM）患者发生神经退行性疾病（ND）风险之间的关系。
设计/设置/参与者：本回顾性纵向队列研究使用退伍军人事务部电子病历数据库，调查了美国老年 T2DM 合并胰岛素治疗的退伍军人中，二甲双胍暴露时长对 ND 的影响。
主要临床结局定义为随访期间诊断为 ND，包括痴呆、阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和轻度认知障碍。次要临床结局分别通过 AD、PD、HD、痴呆和轻度认知障碍进行测量。
经倾向评分权重调整后，共纳入 5528 例患者（平均年龄 63.2±10.9 岁；男性占 98%；白人占 60%），中位随访时间为 5.2 年。排除基线时患有 ND 或其他精神障碍或研究期间胰岛素使用不足三分之二的患者。接受二甲双胍治疗的患者 ND 发生率为 11.48/1000 人年，而未接受二甲双胍治疗的患者为 25.45/1000 人年。与未使用二甲双胍相比，2-4 年和>4 年的二甲双胍暴露与 ND 风险降低显著相关（调整后的 HR（aHR）=0.62，95%CI 0.45 至 0.85；aHR=0.19，95%CI 0.12 至 0.31），而前 2 年的二甲双胍暴露无显著影响。
我们的结论是，长期二甲双胍治疗（>2 年）与老年 T2DM 退伍军人 ND 发生率降低相关。我们需要进行一项具有更具代表性人群和更稳健方法的研究，以进行因果推断。需要进一步研究涉及的机制，并进行随机试验以确认二甲双胍的潜在神经保护作用。
