胰高血糖素样肽-1受体激动剂与糖尿病中的胰腺β细胞凋亡：一项临床前研究的系统评价和荟萃分析

GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies.

作者信息

Rea Nicolas, Ramdass Prakash V A K

机构信息

Department of Public Health and Preventive Medicine, St. George's University School of Medicine, St. George, Grenada.

出版信息

Front Clin Diabetes Healthc. 2025 Aug 27;6:1579961. doi: 10.3389/fcdhc.2025.1579961. eCollection 2025.

INTRODUCTION

Diabetes mellitus (DM) is a global health challenge characterized by progressive beta cell dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as promising therapies, enhancing insulin secretion while potentially preserving beta cell mass by inhibiting apoptosis. However, concerns persist regarding long-term beta cell adaptation and functional exhaustion. This meta-analysis synthesizes preclinical evidence to evaluate the effects of GLP-1RAs on beta cell apoptosis in DM.

METHODS

Following PRISMA guidelines, we systematically searched Scopus, PubMed, Embase, and Google Scholar for preclinical studies assessing GLP-1RAs effects on human beta cell apoptosis. Five studies met inclusion criteria for meta-analysis. Data were extracted on apoptotic rates, and risk of bias was assessed using the OHAT tool. A random-effects model calculated pooled mean differences (MDs) in apoptosis, with sensitivity analyses and funnel plots evaluating robustness and publication bias.

RESULTS

GLP-1RAs significantly reduced beta cell apoptosis (pooled MD: -0.10; 95% CI: -0.15 to -0.05, p = 0.0003), with high heterogeneity (I² = 100%). Sensitivity analyses confirmed consistency, with effect estimates ranging from -0.077 to -0.118 upon sequential study exclusion. Funnel plot and Egger's test (p = 0.80) indicated no significant publication bias, though limited study numbers constrain power.

CONCLUSIONS

GLP-1RAs demonstrate a robust anti-apoptotic effect on pancreatic beta cells in preclinical models, supporting their role in preserving beta cell mass. However, extreme heterogeneity and unresolved questions about long-term functional exhaustion warrant cautious interpretation. Future research should prioritize longitudinal human studies to assess clinical relevance and optimize therapeutic strategies. Introduction.

SYSTEM REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024516313, identifier CRD42024516313.

引言

糖尿病（DM）是一项全球性的健康挑战，其特征为胰岛β细胞功能进行性衰退。胰高血糖素样肽-1受体激动剂（GLP-1RAs）已成为颇具前景的治疗方法，可增强胰岛素分泌，同时可能通过抑制细胞凋亡来维持β细胞数量。然而，对于β细胞的长期适应性和功能耗竭仍存在担忧。本荟萃分析综合临床前证据，以评估GLP-1RAs对糖尿病中β细胞凋亡的影响。

方法

按照PRISMA指南，我们系统检索了Scopus、PubMed、Embase和谷歌学术，查找评估GLP-1RAs对人β细胞凋亡影响的临床前研究。五项研究符合荟萃分析的纳入标准。提取了凋亡率数据，并使用OHAT工具评估偏倚风险。采用随机效应模型计算凋亡的合并平均差（MDs），并通过敏感性分析和漏斗图评估稳健性和发表偏倚。

结果

GLP-1RAs显著降低了β细胞凋亡（合并MD：-0.10；95%CI：-0.15至-0.05，p = 0.0003），异质性较高（I² = 100%）。敏感性分析证实了结果的一致性，逐一排除研究后效应估计值范围为-0.077至-0.118。漏斗图和Egger检验（p = 0.80）表明无显著发表偏倚，尽管研究数量有限限制了效能。