Metformin as an Adjunct in Periodontal Therapy: Mechanistic Insights, Research Evidence and Current Challenges

Periodontal disease is a chronic inflammatory disorder that gradually destroys tooth-supporting tissues including the alveolar bone, periodontal ligament, and cementum. In recent years, interest has grown in repurposing metformin, a well-known oral antidiabetic drug, as an adjunct to periodontal therapy. Experimental studies have indicated that metformin can aid periodontal healing by promoting stem cell-driven regeneration, enhancing osteoblast activity, and reducing osteoclast-mediated resorption. Clinical trials have further reported that both systemic and local applications of metformin, when used alongside conventional non-surgical treatment, can improve probing depth, clinical attachment, and radiographic markers of bone recovery. However, the results remain inconsistent across study designs, dosage strategies, and delivery methods, and concerns about safety and long-term outcomes persist. This review examines the potential role of metformin in periodontal therapy, with a focus on its mechanisms of action, clinical and experimental evidence, and the current challenges of its use in periodontology. Overall, metformin shows promise as a host-modulatory and regenerative adjunct in periodontal therapy, warranting further large-scale clinical trials.