Sun Mingyang, Wang Xiaoling, Lu Zhongyuan, Yang Yitian, Lv Shuang, Miao Mengrong, Chen Wan-Ming, Wu Szu-Yuan, Zhang Jiaqiang
Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Academy of Medical Sciences of Zhengzhou University, Zhengzhou, Henan, China.
Diabetes Metab. 2025 Mar;51(2):101623. doi: 10.1016/j.diabet.2025.101623. Epub 2025 Feb 12.
Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce.
SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89-0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84-0.95) and AD (HR, 0.90; 95 % CI, 0.86-0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92-0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91-1.01).
In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.
2型糖尿病（T2DM）与痴呆风险升高相关，包括阿尔茨海默病（AD）和血管性痴呆（VaD）。虽然钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂和胰高血糖素样肽1（GLP-1）受体激动剂已显示出神经保护潜力，但关于它们在预防痴呆方面疗效的比较数据仍然很少。
我们使用TriNetX数据库进行了一项回顾性队列研究，纳入了307103名使用SGLT2抑制剂的T2DM患者和348686名使用GLP-1受体激动剂的T2DM患者。倾向评分匹配产生了221883对基线特征均衡的患者。主要结局是总体痴呆发病率，次要结局包括AD、VaD和全因死亡率。使用Cox比例风险模型计算风险比（HRs）。
与GLP-1受体激动剂相比，SGLT2抑制剂与总体痴呆发病率显著降低相关（2.7%对3.6%；HR，0.92；95%CI，0.89-0.95）。SGLT2抑制剂也降低了VaD（HR，0.89；95%CI，0.84-0.95）和AD（HR，0.90；95%CI，0.86-0.94）的风险。SGLT2组的全因死亡率较低（3.6%对4.6%；HR，0.95；95%CI，0.92-0.98）。在其他痴呆亚型中未观察到显著差异（HR，0.96；95%CI，0.91-1.01）。
在这个大型的真实世界队列中，SGLT2抑制剂在降低T2DM患者的总体痴呆、VaD和AD风险方面显示出优于GLP-1受体激动剂的疗效。这些发现支持在该人群中优先使用SGLT2抑制剂来降低痴呆风险，不过仍需进行随机对照试验来证实。
