Li Zonglin, Lin Chu, Cai Xiaoling, Lv Fang, Yang Wenjia, Ji Linong
Department of Endocrinology and Metabolism, Peking University People's Hospital, 100044 No.11 Xizhimen South Street, Xicheng District, Beijing China, 100044, People's Republic of China.
Alzheimers Res Ther. 2024 Dec 23;16(1):272. doi: 10.1186/s13195-024-01645-y.
To evaluate the association between anti-diabetic agents and the risks of dementia in patients with type 2 diabetes (T2D).
Literature retrieval was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov between January 1995 and October 2024. Observational studies and randomized controlled trials (RCTs) in patients with T2D, which intercompared anti-diabetic agents or compared them with placebo, and reported the incidence of dementia were included. Conventional and network meta-analyses of these studies were implemented. Results were exhibited as the odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI).
A total of 41 observational studies (3,307,483 participants) and 23 RCTs (155,443 participants) were included. In the network meta-analysis of observational studies, compared with non-users, sodium glucose cotransporter-2 inhibitor (SGLT-2i) (OR = 0.56, 95%CI, 0.45 to 0.69), glucagon-like peptide-1 receptor agonist (GLP-1RA) (OR = 0.58, 95%CI, 0.46 to 0.73), thiazolidinedione (TZD) (OR = 0.68, 95%CI, 0.57 to 0.81) and metformin (OR = 0.89, 95%CI, 0.80 to 0.99) treatments were all associated with reduced risk of dementia in patients with T2D. The surface under the cumulative ranking curve (SUCRA) evaluation conferred a rank order as SGLT-2i > GLP-1RA > TZD > dipeptidyl peptidase-4 inhibitor (DPP-4i) > metformin > α-glucosidase inhibitor (AGI) > glucokinase activator (GKA) > sulfonylureas > glinides > insulin in terms of the cognitive benefits. Meanwhile, compared with non-users, SGLT-2i (OR = 0.43, 95%CI, 0.30 to 0.62), GLP-1RA (OR = 0.54, 95%CI, 0.30 to 0.96) and DPP-4i (OR = 0.73, 95%CI, 0.57 to 0.93) were associated with a reduced risk of Alzheimer's disease while a lower risk of vascular dementia was observed in patients receiving SGLT-2i (OR = 0.42, 95%CI, 0.22 to 0.80) and TZD (OR = 0.52, 95%CI, 0.36 to 0.75) treatment. In the network meta-analysis of RCTs, the risks of dementia were comparable among anti-diabetic agents and placebo.
Compared with non-users, SGLT-2i, GLP-1RA, TZD and metformin were associated with the reduced risk of dementia in patients with T2D. SGLT-2i, and GLP-1RA may serve as the optimal choice to improve the cognitive prognosis in patients with T2D.
评估2型糖尿病（T2D）患者中抗糖尿病药物与痴呆风险之间的关联。
于1995年1月至2024年10月期间在PubMed、Embase、Cochrane对照试验中央注册库和Clinicaltrial.gov进行文献检索。纳入了对T2D患者进行抗糖尿病药物相互比较或与安慰剂比较并报告痴呆发病率的观察性研究和随机对照试验（RCT）。对这些研究进行传统和网状荟萃分析。结果以比值比（OR）或风险比（RR）及95%置信区间（CI）表示。
共纳入41项观察性研究（3307483名参与者）和23项RCT（155443名参与者）。在观察性研究的网状荟萃分析中，与未使用者相比，钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）（OR = 0.56，95%CI，0.45至0.69）、胰高血糖素样肽-1受体激动剂（GLP-1RA）（OR = 0.58，95%CI，0.46至0.73）、噻唑烷二酮类（TZD）（OR = 0.68，95%CI，0.57至0.81）和二甲双胍（OR = 0.89，95%CI，0.80至0.99）治疗均与T2D患者痴呆风险降低相关。累积排序曲线下面积（SUCRA）评估显示，就认知益处而言，排序为SGLT-2i > GLP-1RA > TZD > 二肽基肽酶-4抑制剂（DPP-4i） > 二甲双胍 > α-葡萄糖苷酶抑制剂（AGI） > 葡萄糖激酶激活剂（GKA） > 磺脲类 > 格列奈类 > 胰岛素。同时，与未使用者相比，SGLT-2i（OR = 0.43，95%CI，0.30至0.62）、GLP-1RA（OR = 0.54，95%CI，0.30至0.96）和DPP-4i（OR = 0.73，95%CI，0.57至0.93）与阿尔茨海默病风险降低相关，而接受SGLT-2i（OR = 0.42，95%CI，0.22至0.80）和TZD（OR = 0.52，95%CI，0.36至0.75）治疗的患者血管性痴呆风险较低。在RCT的网状荟萃分析中，抗糖尿病药物与安慰剂之间的痴呆风险相当。
与未使用者相比，SGLT-2i、GLP-1RA、TZD和二甲双胍与T2D患者痴呆风险降低相关。SGLT-2i和GLP-1RA可能是改善T2D患者认知预后的最佳选择。
