{"title":"GLP-1受体激动剂与糖尿病胰腺β细胞凋亡：临床前研究的系统回顾和荟萃分析","authors":"Nicolas Rea, Prakash V A K Ramdass","doi":"10.3389/fcdhc.2025.1579961","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>System review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024516313, identifier CRD42024516313.</p>","PeriodicalId":73075,"journal":{"name":"Frontiers in clinical diabetes and healthcare","volume":"6 ","pages":"1579961"},"PeriodicalIF":2.2000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420244/pdf/","citationCount":"0","resultStr":"{\"title\":\"GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies.\",\"authors\":\"Nicolas Rea, Prakash V A K Ramdass\",\"doi\":\"10.3389/fcdhc.2025.1579961\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>System review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024516313, identifier CRD42024516313.</p>\",\"PeriodicalId\":73075,\"journal\":{\"name\":\"Frontiers in clinical diabetes and healthcare\",\"volume\":\"6 \",\"pages\":\"1579961\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420244/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in clinical diabetes and healthcare\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/fcdhc.2025.1579961\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in clinical diabetes and healthcare","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fcdhc.2025.1579961","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies.
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.
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