Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis.
Metformin Use Associated with Reduced Risk of Dementia in Patients with Diabetes: A Systematic Review and Meta-Analysis.
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DOI：
10.3233/jad-180263
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Aromataris E
中科院分区：
文献类型：
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作者：
Campbell JM;Stephenson MD;de Courten B;Chapman I;Bellman SM;Aromataris E
二甲双胍是一线抗高血糖药物，是一种 AMPK 激活剂，并被假设可充当老年保护剂。关于其与年龄相关认知能力下降的各种分类的关系的研究显示出积极和消极的结果。综合关于二甲双胍使用与痴呆风险、进展和严重程度之间关系的最佳现有证据。符合条件的研究调查了与任何未接受二甲双胍治疗的对照组相比，二甲双胍对痴呆症、阿尔茨海默病或任何认知障碍指标的影响。初步检索共获得 862 条引用，其中包括 14 项研究（7 项队列研究、4 项横断面研究、2 项随机对照试验和一项病例对照研究）。三项研究的荟萃分析显示，糖尿病二甲双胍治疗后认知障碍的发生率显着降低（比值比 = 0.55，95% CI 0.38至0.78），而六项研究表明痴呆发生率也显着降低（风险比 = 0.76，95% CI 0.39至0.88）。尽管两项随机对照试验均表明二甲双胍与安慰剂相比具有神经保护作用，但简易精神状态检查分数并未受到二甲双胍使用的显着影响。一些研究发现糖尿病患者使用二甲双胍会产生负面或中性影响。讨论了二甲双胍引起的维生素 B12 缺乏的潜在机制。二甲双胍应继续用作有痴呆或阿尔茨海默病风险的糖尿病患者的一线治疗。现有证据不支持非糖尿病患者使用二甲双胍来预防痴呆症。
Metformin, a first line antihyperglycemic medication, is an AMPK activator and has been hypothesized to act as a geroprotective agent. Studies on its association with various classifications of age-related cognitive decline have shown mixed results with positive and negative findings. To synthesize the best available evidence on the association of metformin-use with risk, progression, and severity of dementia. Eligible research investigated the effect of metformin on dementia, Alzheimer’s disease, or any measure of cognitive impairment compared to any control group who were not receiving metformin. The initial search resulted in 862 citations from which 14 studies (seven cohort, four cross-sectional, two RCTs, and one case control) were included. Meta-analysis of three studies showed that cognitive impairment was significantly less prevalent in diabetic metformin (Odds ratio = 0.55, 95% CI 0.38 to 0.78), while six studies showed that dementia incidence was also significantly reduced (Hazard ratio = 0.76, 95% CI 0.39 to 0.88). Mini-Mental State Examination scores were not significantly affected by metformin-use, although both RCTs showed that metformin had a neuroprotective effect compared to placebo. Some studies found negative or neutral effects for metformin use by people with diabetes; the potential mechanism of metformin-induced vitamin B12 deficiency is discussed. Metformin should continue to be used as a first line therapy for diabetes in patients at risk of developing dementia or Alzheimer’s disease. The use of metformin by individuals without diabetes for the prevention of dementia is not supported by the available evidence.