Background

Dementia is more prevalent among people with type 2 diabetes, but little is known regarding the influence of antidiabetic agents on this association.

Objective

This study assessed the impact of various antidiabetic agents on the risk of dementia among patients with Type 2 diabetes mellitus.

Methods

Relevant studies were retrieved from the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. Nine antidiabetic agents were included in the search. Data were pooled via network meta-analysis and meta-analysis.

Results

Nine studies were selected for the network meta-analysis with 530,355 individuals and 17 studies for the meta-analysis with 1,258,879 individuals. The analysis excluded glucagon-like peptide 1 (GLP-1) analogs and sodium-dependent glucose transporter 2 (SGLT-2) inhibitors due to the absence of relevant data. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0.54; 95% confidence interval [CI], 0.38–0.74, HR for metformin, 0.75; 95% CI, 0.63–0.86; HR for sulfonylurea, 0.85; 95%CI, 0.73–0.98 and HR for thiazolidinedione, 0.70; 95% CI, 0.55–0.89, respectively). However, the node-splitting analysis showed the inconsistency of direct and indirect estimates in sulfonylurea (P = 0.042). DPP-4 inhibitors, metformin, thiazolidinedione, and sulfonylurea exhibited a significant impact on the risk of dementia in diabetics compared with insulin (HR, 0.35; 95%CI, 0.20–0.59, HR, 0.48; 95% CI, 0.30–0.77, HR, 0.45; 95% CI, 0.29–0.73 and HR, 0.55; 95% CI, 0.34–0.88, respectively). DPP-4 inhibitors also exhibited a protective effect on the risk of Alzheimer's dementia compared with the no treatment with antidiabetic agents (HR, 0.48; 95% CI, 0.25–0.92). The meta-analysis demonstrated a protective effect of using metformin and DPP-4 inhibitors on the risk of dementia (HR, 0.86; 95% CI, 0.74–1.00 and HR, 0.65; 95% CI, 0.55–0.76, respectively). Further analysis showed insulin was associated with an increased risk of Alzheimer's dementia (HR, 1.60; 95% CI, 1.13–2.26). Only two case-control studies mentioned GLP-1 analogs and SGLT-2 inhibitors, and the pooled ORs showed no evidence of an association with dementia (GLP-1 analogs: 0.71; 95% CI, 0.46–1.10 and SGLT-2 inhibitors: 0.74; 95% CI, 0.47–1.15).

Conclusion

This analysis indicated that patients with type 2 diabetes under treatment with DPP-4 inhibitors presented with the lowest risk of dementia, followed by those treated with metformin and thiazolidinedione, while treatment with insulin was associated with the highest risk. For the increasing focus on the protective effect on dementia, further specific clinical studies are needed to evaluate the impact of GLP-1 analogs and SGLT-2 inhibitors on the risk of dementia.

中文翻译：

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抗糖尿病药对痴呆症风险的影响：贝叶斯网络荟萃分析。

背景

痴呆症在2型糖尿病患者中更为普遍，但对于抗糖尿病药对此关联的影响知之甚少。

目的

这项研究评估了2型糖尿病患者中各种抗糖尿病药对痴呆症风险的影响。

方法

相关研究从PubMed，Embase，Cochrane对照试验中央注册中心（CENTRAL）和ClinicalTrials.gov数据库中检索。搜索中包括九种抗糖尿病药。通过网络荟萃分析和荟萃分析合并数据。

结果

选择了9项研究进行了530,355个人的网络荟萃分析，选择了17项研究进行了1,258,879个体的荟萃分析。由于缺乏相关数据，该分析排除了胰高血糖素样肽1（GLP-1）类似物和钠依赖性葡萄糖转运蛋白2（SGLT-2）抑制剂。与不使用抗糖尿病药治疗相比，使用二肽基肽酶-4（DPP-4）抑制剂，二甲双胍，噻唑烷二酮和磺酰脲与痴呆风险降低相关（DPP-4抑制剂的危险比[HR]为0.54； 95％置信区间[CI]为0.38-0.74，二甲双胍的HR为0.75； 95％CI为0.63-0.86；磺酰脲的HR为0.85；噻唑烷二酮的HR为0.73-0.98； HR为0.70； 95％CI分别为0.55-0.89）。然而，节点分解分析显示磺脲类药物的直接和间接估计值不一致（P = 0.042）。与胰岛素相比，DPP-4抑制剂，二甲双胍，噻唑烷二酮和磺酰脲对糖尿病患者的痴呆风险有显着影响（HR，0.35； 95％CI，0.20-0.59，HR，0.48； 95％CI，0.30-0.77， HR：0.45； 95％CI：0.29–0.73； HR：0.55； 95％CI：0.34-0.88）。与不使用抗糖尿病药进行治疗相比，DPP-4抑制剂还显示出对阿尔茨海默氏痴呆风险的保护作用（HR，0.48； 95％CI，0.25-0.92）。荟萃分析表明，使用二甲双胍和DPP-4抑制剂对痴呆风险具有保护作用（HR，0.86； 95％CI，0.74-1.00； HR，0.65； 95％CI，0.55-0.76）。进一步的分析表明，胰岛素与阿尔茨海默氏痴呆症的风险增加有关（HR，1.60； 95％CI，1.13-2.26）。只有两项病例对照研究提到了GLP-1类似物和SGLT-2抑制剂，合并的ORs没有显示与痴呆症相关的证据（GLP-1类似物：0.71； 95％CI，0.46-1.10和SGLT-2抑制剂： 0.74； 95％CI，0.47-1.15）。

结论

该分析表明，接受DPP-4抑制剂治疗的2型糖尿病患者患痴呆症的风险最低，其次是二甲双胍和噻唑烷二酮治疗的患者，而胰岛素治疗的患病风险最高。为了越来越关注痴呆的保护作用，需要进一步的具体临床研究来评估GLP-1类似物和SGLT-2抑制剂对痴呆风险的影响。