EFFECTS OF GLP-1 RECEPTOR AGONISTS ON PERIODONTAL HEALTH, ORAL WOUND HEALING, AND PERIODONTAL REGENERATION: A SYSTEMATIC REVIEW OF PRECLINICAL EVIDENCE

Abstract

Background: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the tooth-supporting tissues and is strongly associated with metabolic disorders such as type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1Ras) have demonstrated anti-inflammatory, osteoprotective, and regenerative properties beyond glycemic control, suggesting potential applications in periodontal therapy. This systematic review aimed to evaluate the available preclinical evidence regarding the effects of GLP-1Ras on periodontal health, oral wound healing, and periodontal regeneration.

Methods: A systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, ScienceDirect, and the Cochrane Library were searched from inception to June 2026. Experimental animal and in vitro studies evaluating GLP-1Ras on periodontal inflammation, oral wound healing, alveolar bone preservation, and periodontal regeneration were included. Methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist.

Results: Three preclinical studies met the eligibility criteria, including one animal study and two in vitro investigations. Liraglutide and exendin-4 consistently reduced periodontal inflammation, suppressed pro-inflammatory cytokines, decreased osteoclast activity, preserved alveolar bone, enhanced osteogenic differentiation, promoted periodontal ligament cell proliferation and migration, and activated regenerative signaling pathways, including MAPK and Wnt signaling. All included studies demonstrated satisfactory methodological quality.

Conclusion: Current preclinical evidence suggests that GLP-1Ras possess significant anti-inflammatory, osteoprotective, and regenerative properties that may improve periodontal health and oral wound healing. However, the evidence is limited to experimental studies, and well-designed clinical trials are required to establish their efficacy and safety before routine application in periodontal practice