韩国首尔国立大学盆塘医院Eun Ha Kang团队研究了钠葡萄糖协同转运蛋白-2抑制剂与老年痴呆症风险的相关性。这一研究成果于2024年8月28日发表在《英国医学杂志》上。

为了比较40~69岁2型糖尿病患者与钠葡萄糖协同转运蛋白-2（SGLT-2）抑制剂和二肽基肽酶-4（DPP-4）抑制剂相关的痴呆风险，研究组根据2013-2021韩国国民健康保险服务数据，进行了一项基于人群的队列研究，涉及110885例由倾向评分匹配的年龄在40-69岁之间的2型糖尿病成年人，他们开始使用SGLT-2抑制剂或DPP-4抑制剂。

主要结局是新发痴呆症。次要结局是需要药物治疗的痴呆症和个体类型的痴呆症，包括阿尔茨海默病和血管性痴呆。对照结果为生殖器感染（阳性）、骨关节炎相关临床病例和白内障手术（阴性）。使用Cox模型估计危险比和95%置信区间（CI）。进行了随访时间分层分析（>2年和≤2年）和按年龄、性别、二甲双胍合并使用和基线心血管风险进行的亚组分析。

研究组对110885例开始接受SGLT-2抑制剂或DPP-4抑制剂的参与者进行了平均670天（标准差650）的倾向评分匹配随访，产生了1172名新诊断的痴呆症患者：SGLT-2抑制者的发病率为每100人-年0.22例，DPP-4抑制者为每100人-年0.35例，痴呆症的风险比为0.65（95%CI 0.58至0.73），需要药物的痴呆症为0.54（0.46至0.63），阿尔茨海默病为0.61（0.53至0.69），血管性痴呆症为0.48（0.33至0.70）。生殖器感染的对照结果风险比为2.67（2.57至2.77），骨关节炎为0.97（0.95至0.98），白内障手术为0.92（0.89至0.96）。当对白内障手术测量的残余混杂因素进行校准时，痴呆症的风险比为0.70（0.62至0.80）。治疗两年以上（痴呆症的危险比为0.57，95%CI为0.46至0.70）比治疗两年或更短（0.52，0.41至0.66）的相关性更大，并且在各亚组中持续存在。

研究组表明，SGLT-2抑制剂可能预防痴呆，治疗时间越长，效果越好。由于这项研究是观察性的，因此容易产生残余混杂和信息审查，因此可能高估了效应大小。需要随机对照试验来证实这些发现。

附：英文原文

Title: Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study

Author: Anna Shin, Bo Kyung Koo, Jun Young Lee, Eun Ha Kang

Issue&Volume: 2024/08/28

Abstract:

Objective To compare the risk of dementia associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in adults aged 40-69 years with type 2 diabetes.

Design Population based cohort study.

Setting Korean National Health Insurance Service data, 2013-21.

Participants 110885 propensity score matched pairs of adults with type 2 diabetes aged 40-69 years who were initiators of either an SGLT-2 inhibitor or a DPP-4 inhibitor.

Main outcome measures The primary outcome was new onset dementia. Secondary outcomes were dementia requiring drug treatment and individual types of dementia, including Alzheimer’s disease and vascular dementia. Control outcomes were genital infections (positive), and osteoarthritis related clinical encounters and cataract surgery (negative). Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox models. Follow-up time stratified analyses (>2 years and ≤2 years) and subgroup analyses by age, sex, concomitant use of metformin, and baseline cardiovascular risk were performed.

Results 110885 propensity score matched pairs of initiators of an SGLT-2 inhibitor or a DPP-4 inhibitor were followed-up for a mean 670 (standard deviation 650) days, generating 1172 people with newly diagnosed dementia: incidence rate 0.22 per 100 person years in initiators of SGLT-2 inhibitors and 0.35 per 100 person years in initiators of DPP-4 inhibitors, with hazard ratios of 0.65 (95% CI 0.58 to 0.73) for dementia, 0.54 (0.46 to 0.63) for dementia requiring drugs, 0.61 (0.53 to 0.69) for Alzheimer’s disease, and 0.48 (0.33 to 0.70) for vascular dementia. The hazard ratios for the control outcomes were 2.67 (2.57 to 2.77) for genital infections, 0.97 (0.95 to 0.98) for osteoarthritis related encounters, and 0.92 (0.89 to 0.96) for cataract surgery. When calibrated for residual confounding measured by cataract surgery, the hazard ratio for dementia was 0.70 (0.62 to 0.80). The association was greater for more than two years of treatment (hazard ratio of dementia 0.57, 95% CI 0.46 to 0.70) than for two years or less (0.52, 0.41 to 0.66) and persisted across subgroups.

Conclusion SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment. As this study was observational and therefore prone to residual confounding and informative censoring, the effect size could have been overestimated. Randomised controlled trials are needed to confirm these findings.

DOI: 10.1136/bmj-2024-079475

Source: https://www.bmj.com/content/386/bmj-2024-079475