Preclinical Evidence Suggests GLP-1RAs Reduce Periodontal Inflammation and Bone Loss via `NF-κB`/`Wnt` Pathways

Both diabetes mellitus and periodontal disease are highly prevalent chronic conditions, intricately linked by shared inflammatory and oxidative stress pathways. Current treatments for periodontal disease often focus on mechanical debridement and antibiotics, which may not fully address the systemic inflammatory component, especially in diabetic patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), primarily known for their role in type 2 diabetes mellitus and obesity management, possess well-documented anti-inflammatory properties. This review explores the hypothesis that these agents could offer a novel therapeutic avenue for periodontal tissues by modulating inflammation and bone metabolism.

Following the Joanna Briggs Institute methodology and PRISMA-ScR extension, a systematic search was conducted across PubMed/MEDLINE, Web of Science, Scopus, Embase, LILACS, and the Cochrane Library. The search targeted studies evaluating the impact of GLP-1 receptor agonists on periodontal models or tissues, without date restriction. Records were screened against predefined eligibility criteria, and data were charted using a structured extraction form. This comprehensive review ultimately included 7 studies, comprising 3 animal studies, 3 in vitro studies, and 1 mixed-design study, all published between 2015 and 2022.

The scoping review identified seven studies, published between 2015 and 2022, comprising three animal studies, three in vitro studies, and one mixed-design study. Notably, no clinical trials evaluating GLP-1RAs for periodontal tissue effects were found. Liraglutide was the most frequently investigated agent, featured in four out of seven studies.

GLP-1 receptor agonists were consistently associated with reduced pro-inflammatory signaling, attenuated alveolar bone resorption, and enhanced osteogenic differentiation across the included preclinical models. These beneficial effects were frequently mediated through the NF-κB/MAPK and Wnt/β-catenin pathways, indicating a direct molecular mechanism of action. One study specifically reported reduced inflammatory markers without a corresponding reduction in bone loss, highlighting some variability in outcomes and the complexity of the disease pathways involved.