二肽基肽酶-4 抑制剂对 2 型糖尿病患者肿瘤坏死因子-α水平的影响。

Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus.

机构信息

Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.

出版信息

Eur J Med Res. 2024 Jul 12;29(1):363. doi: 10.1186/s40001-024-01955-9.

DOI:10.1186/s40001-024-01955-9

PMID:38997754

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11241791/

Abstract

AIMS

Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM.

METHODS

PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0.

RESULTS

Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, - 0.70, 95% CI - 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, - 4.50 pg/mL, 95% CI - 4.68 to - 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI - 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration.

CONCLUSIONS

A significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM. Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479.

摘要

目的

二肽基肽酶-4 抑制剂（DPP-4i）是治疗 2 型糖尿病（T2DM）的口服抗糖尿病药物。尽管已经确定了其对葡萄糖稳态的作用，但尚未建立 DPP-4i 治疗期间肿瘤坏死因子 alpha（TNF-alpha）水平变化的全面说明。本研究旨在探讨 DPP-4i 对 T2DM 患者 TNF-alpha 的抗炎作用。

方法

系统检索 PubMed、Embase 和 Cochrane Library 从成立到 2024 年 5 月 31 日的文献。确定了探讨 DPP-4i 对 TNF-alpha 水平影响的随机对照试验。根据 Cochrane 标准评估偏倚风险。如果存在异质性，则选择固定或随机效应模型来汇总估计值。进行亚组分析以探讨影响异质性的潜在因素。使用 Revman 5.3 和 STATA 12.0 软件进行相关的荟萃分析。

结果

纳入了 11 项涉及 884 名 T2DM 患者的试验。汇总估计表明，DPP-4i 对 T2DM 患者的 TNF-alpha 水平没有显著调节作用（WMD，-0.70，95%CI-1.94 至 0.53，P=0.26）。与安慰剂相比，DPP-4i 对 TNF-alpha 有显著影响（WMD，-4.50pg/mL，95%CI-4.68 至-4.32，P<0.00001），与活性药物相比，也表现出类似的影响（WMD，0.10pg/mL，95%CI-0.11 至 0.30，P=0.35）。根据敏感性测试，估计值是稳定的。亚组分析表明，异质性可能与基线糖化血红蛋白（HbA1c）、年龄或治疗持续时间无关。

结论

与安慰剂相比，DPP-4i 对 T2DM 患者的 TNF-alpha 水平有显著影响。与活性对照药物相比，DPP-4i 对 TNF-alpha 没有显著影响。应进行更多的大样本研究，以说明 DPP-4i 对 T2DM 患者 TNF-alpha 水平的影响。试验注册国际前瞻性系统评价注册（PROSPERO）编号：CRD42020185479。