GLP-1 Receptor Agonists in Periodontology: Mechanisms, Clinical Evidence, and Implications for Care.

GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity and are increasingly relevant in periodontal and implant practice. This review covers mechanisms, preclinical and early human evidence, and practical periodontal considerations; the structured database search is conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) and the International Committee of Medical Journal Editors (ICMJE) principles. Two pathways explain GLP-1RAs' relevance: indirect effects from better glycemic control, weight loss, and reduced inflammation; and direct tissue effects involving GLP-1R signaling and the GLP-1/dipeptidyl peptidase-4 (DPP-4) axis. Preclinical studies show reduced inflammation, osteoclast activity, and alveolar bone loss, along with improved periodontal stem cell function under hyperglycemia or inflammation via Nuclear Factor-kappaB (NF-kappaB), Wingless-related integration site (Wnt)/beta-catenin, and Mitogen-Activated Protein Kinase (MAPK) pathways. Animal studies on implants and local delivery, including exendin-4 platforms, suggest osteometabolic benefits. Human data are limited and mostly observational, and confounders include metabolic status, smoking, medication, and nutrition. Oral side effects such as xerostomia and dehydration are also noted. At present, GLP-1RA therapy should be regarded as a contextual modifier of periodontal risk and healing capacity rather than as a stand-alone periodontal therapy.