Orkaby Ariela R, Cho Kelly, Cormack Jean, Gagnon David R, Driver Jane A
From the VA Boston Geriatric Research, Education, and Clinical Center (GRECC) and Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) (A.R.O., K.C., J.C., D.R.G., J.A.D.); Division of Aging (A.R.O., K.C., J.A.D.), Brigham & Women's Hospital, Harvard Medical School; and Boston University School of Public Health Department of Biostatistics (D.R.G.), MA.
Neurology. 2017 Oct 31;89(18):1877-1885. doi: 10.1212/WNL.0000000000004586. Epub 2017 Sep 27.
To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.
This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.
We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61-0.73) and 0.78 (95% CI 0.72-0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79-0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87-1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63-0.91), had good renal function (HR 0.86; 95% CI 0.76-0.97), and were white (HR 0.87; 95% CI 0.77-0.99).
After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.
确定二甲双胍与磺脲类药物相比，是否与较低的痴呆发病率相关。
这是一项对年龄≥65岁的美国2型糖尿病退伍军人进行的回顾性队列研究，这些退伍军人是二甲双胍或磺脲类药物的新使用者且无痴呆症。治疗2年后开始随访。为了考虑适应症导致的混杂因素，我们制定了倾向评分（PS）并使用治疗权重逆概率（IPTW）方法。Cox比例风险模型估计了新发痴呆的风险比（HR）。
我们确定了17200名二甲双胍新使用者和11440名磺脲类药物新使用者。平均年龄为73.5岁，平均糖化血红蛋白（HbA1c）为6.8%。在平均5年的随访中，诊断出4906例痴呆病例。由于年龄的效应修正，所有分析均使用年龄分段模型进行。二甲双胍使用者与磺脲类药物使用者相比，任何痴呆的粗风险比[HR]在年龄<75岁和≥75岁的人群中分别为0.67（95%置信区间[CI]0.61 - 0.73）和0.78（95%CI 0.72 - 0.83）。经过PS IPTW调整后，结果在<75岁的退伍军人中仍然显著（HR 0.89；95%CI 0.79 - 0.99），但在≥75岁的人群中不显著（HR 0.96；95%CI 0.87 - 1.05）。在糖化血红蛋白（HbA1C）值≥7%的年轻退伍军人亚组、肾功能良好的亚组以及白人亚组中，也观察到较低的痴呆风险（HR分别为0.76；95%CI 0.63 - 0.91、HR 0.86；95%CI 0.76 - 0.97、HR 0.87；95%CI 0.77 - 0.99）。
在考虑适应症导致的混杂因素后，与使用磺脲类药物相比，二甲双胍在<75岁的退伍军人中与随后发生痴呆的风险较低相关。需要进一步开展工作以确定哪些患者可能从二甲双胍预防痴呆中获益。
