Wu Che-Yuan, Iskander Carina, Wang Christa, Xiong Lisa Y, Shah Baiju R, Edwards Jodi D, Kapral Moira K, Herrmann Nathan, Lanctôt Krista L, Masellis Mario, Swartz Richard H, Cogo-Moreira Hugo, MacIntosh Bradley J, Rabin Jennifer S, Black Sandra E, Saskin Refik, Swardfager Walter
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Diabetes Care. 2023 Feb 1;46(2):297-304. doi: 10.2337/dc22-1705.
Type 2 diabetes (T2D) increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to determine whether new use of sodium-glucose cotransporter 2 (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) inhibitors was associated with lower dementia risk.
Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP-4 inhibitor from 1 July 2016 to 31 March 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer's disease and related dementias. Propensity score-weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and CIs for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed.
Among 106,903 individuals, SGLT2 inhibitors compared with DPP-4 inhibitors were associated with lower risk of dementia (14.2/1,000 person-years; aHR 0.80 [95% CI 0.71-0.89]) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67 [95% CI 0.53-0.84]), followed by empagliflozin (aHR 0.78 [95% CI 0.69-0.89]), whereas canagliflozin showed no association (aHR 0.96 [95% CI 0.80-1.16]). The as-treated analysis observed a larger association (aHR 0.66 [95% CI 0.57-0.76]) than the intention-to-treat analysis.
SGLT2 inhibitors showed an association with lower dementia risk in older people with T2D. Randomized controlled trials are warranted.
2型糖尿病（T2D）会增加患痴呆症的风险，但仍缺乏明确证据来推荐可降低该风险的干预措施。这项基于人群的回顾性队列研究旨在确定，与二肽基肽酶4（DPP-4）抑制剂相比，新使用钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是否与较低的痴呆症风险相关。
2016年7月1日至2021年3月31日期间新使用SGLT2抑制剂或DPP-4抑制剂的安大略省66岁及以上居民进入该队列。使用经过验证的阿尔茨海默病及相关痴呆症算法来识别新发痴呆症。倾向评分加权Cox比例风险模型用于获得新发痴呆症发生时间的调整后风险比（aHR）和置信区间（CI）。为了解决反向因果关系和疾病潜伏期问题，观察窗口从队列进入后1年的滞后时间开始。主要分析遵循意向性治疗暴露定义，并进行了次要的实际治疗分析。
在106,903名个体中，从队列进入开始平均随访2.80年期间，与DPP-4抑制剂相比，SGLT2抑制剂与较低的痴呆症风险相关（14.2/1000人年；aHR 0.80 [95%CI 0.71 - 0.89]）。当按不同的SGLT2抑制剂分层时，达格列净的风险最低（aHR 0.67 [95%CI 0.53 - 0.84]），其次是恩格列净（aHR 0.78 [95%CI 0.69 - 0.89]），而卡格列净未显示出相关性（aHR 0.96 [95%CI 0.80 - 1.16]）。实际治疗分析观察到的相关性（aHR 0.66 [95%CI 0.57 - 0.76]）比意向性治疗分析更大。
SGLT2抑制剂在患有T2D的老年人中显示出与较低的痴呆症风险相关。有必要进行随机对照试验。
