Epidemiology and Biostatistics, The University of Arizona Mel and Enid Zuckerman College of Public Health, Tucson, Arizona, USA.
UA Center for Innovation in Brain Science, The University of Arizona Health Sciences, Tucson, Arizona, USA.
BMJ Open Diabetes Res Care. 2022 Sep;10(5). doi: 10.1136/bmjdrc-2022-002894.
Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET).
This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer's disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models.
Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15).
Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia.
研究表明，降糖药物（ADM）与痴呆风险降低相关，但目前的研究结果并不一致。本研究比较了接受磺酰脲（SU）或噻唑烷二酮（TZD）治疗的 2 型糖尿病（T2D）患者与接受二甲双胍（MET）治疗的 T2D 患者发生痴呆的风险。
这是一项使用退伍军人事务医疗保健系统所有站点的电子病历进行的 2 型糖尿病患者的前瞻性观察性研究。纳入 2001 年 1 月 1 日至 2017 年 12 月 31 日期间起始 ADM 时年龄≥60 岁且无痴呆的 T2D 患者。根据处方记录，组建 SU 单药治疗组、TZD 单药治疗组和对照组（MET 单药治疗组）。要求参与者至少接受指定治疗 1 年。主要结局为全因痴呆，两个次要结局为阿尔茨海默病和血管性痴呆，通过国际疾病分类（ICD）第 9 版或 ICD 第 10 版代码定义。采用倾向评分加权 Cox 比例风险模型比较结局发生风险。
在 559106 名符合条件的退伍军人中（平均年龄 65.7（8.7）岁），全因痴呆发生率为每 1000 人年 8.2 例（95%CI 6.0 至 13.7）。经过至少 1 年的治疗，与 MET 单药治疗相比，TZD 单药治疗可降低 22%的全因痴呆发病风险（HR 0.78，95%CI 0.75 至 0.81），MET 和 TZD 双联治疗可降低 11%（HR 0.89，95%CI 0.86 至 0.93），而 SU 单药治疗的风险则升高 12%（HR 1.12，95%CI 1.09 至 1.15）。
在 T2D 患者中，与 MET 相比，TZD 治疗与痴呆风险降低相关，SU 治疗与痴呆风险升高相关。SU 联合 MET 或 TZD 可能部分抵消其致痴呆前效应。这些发现可能有助于为痴呆风险较高的老年 T2D 患者选择药物。
