SYSTEMATIC REVIEW article
Front. Clin. Diabetes Healthc.
Sec. Diabetes Therapies
Volume 6 - 2025 | doi: 10.3389/fcdhc.2025.1579961
This article is part of the Research TopicPharmaceutical Care and Wellness of DiabetesView all 8 articles
GLP-1 receptor agonists and pancreatic beta cell apoptosis in diabetes mellitus: a systematic review and meta-analysis of preclinical studies
Provisionally accepted
- 1Department of Public Health and Preventive Medicine, School of Medicine, St George's University, True Blue, Grenada
- 2School of Medicine, St George's University, St. George's, Grenada
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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.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.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.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.
Keywords: Diabetes Mellitus, GLP-1 receptor agonists, GLP-1RAs, pancreatic beta cell, Apoptosis, Exenatide, exendin-4
Received: 19 Feb 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Ramdass and Rea. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prakash V.A.K. Ramdass, Department of Public Health and Preventive Medicine, School of Medicine, St George's University, True Blue, Grenada
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