Periodontitis and GLP-1 pathways: a new frontier in oral-systemic health connections —a scoping review

Periodontitis, a chronic inflammatory disease of the periodontium, has well-established links to systemic metabolic conditions, particularly diabetes and obesity. Recent research suggests a novel interaction between periodontitis and glucagon-like peptide-1 (GLP-1) pathways, both of which regulate glucose metabolism and inflammation. In this review, we examine the potential bidirectional relationships between periodontitis and GLP-1 signaling and evaluate the therapeutic implications of GLP-1 receptor agonists (GLP-1 RAs) in periodontal disease. A systematic search of PubMed, Embase, and the Cochrane Library identified 52 studies published between 1990 and 2025, ranging from <i>in vitro</i> and animal studies to human clinical and observational research. Findings indicate a multifaceted relationship between GLP-1 pathways and periodontal disease. Periodontitis may impair GLP-1 signaling and exacerbate glucotoxicity and lipotoxicity in individuals with diabetes or obesity. Several periodontopathic bacteria, notably <i>Porphyromonas gingivalis</i>, produce DPP-4-like enzymes that degrade GLP-1 and potentially disrupt glucose regulation. GLP-1 RAs, such as liraglutide and exendin-4, demonstrated anti-inflammatory, osteoprotective, and regenerative effects in preclinical models. Additionally, studies identified host and microbial DPP-4 activity as key mechanistic links between periodontal inflammation and systemic insulin resistance. This review highlights a novel and clinically relevant intersection between periodontitis and GLP-1 biology. GLP-1 RAs and DPP-4 inhibitors may offer dual benefits for metabolic control and periodontal health. Further research is needed to define delivery strategies, assess efficacy across patient populations, and explore the therapeutic targeting of DPP-4 activity in both host and microbial contexts.