Discussion
age-associated diseases, periodontitis, inflammation, gingivitis, PD, diabetic
CHRONIC GINGIVITIS, INFLAMMATION, PERIODONTITIS, AIDS, GINGIVITIS, PERIODONTAL DISEASE, PERIODONTITIS, PATHOGENESIS, INFLAMMATORY RESPONSE
Glucose metabolism is widely known to directly impact PD progression [Periodontitis and gingivitis differ in the destruction of supporting periodontal tissues that is irreversible upon removal of microbial challenge. However, the trigger for progression from a stable chronic gingivitis to destructive periodontitis remains unclear [Unfortunately, testing the same in vivo approach of bacteria-led gingival inflammation in patients (experimental gingivitis model) would not be ethical as systemic Metformin has never been used in the management of PD. Therefore, we developed the first trial to repurpose systemic Metformin as an adjunct to periodontal disease treatment, as a first step to investigate the potential use of Metformin in PD management. We showed that Metformin aids on control of systemic and local inflammatory response after treatment leading to a mild improvement in clinical periodontal parameters. Although we had a low n number (leaving the trial underpowered) and the medication was prescribed for only 10 days, the results were surprisingly satisfactory, giving signs of effectiveness of potential benefits of Metformin use as an adjunct to periodontal treatment. Another important consideration of our trial is the Metformin dose chosen. Our animals were administered a dose reported as the optimal oral dose for human diabetic treatment (1200 mg/60 kg/day) that resulted in enhancement of longevity [The optimal concentrations of systemic antibiotics used as adjuncts to PD management have been reported to improve PPD from a rage of 0.26–0.53 mm when taken after subgingival instrumentation [Long-term use of Metformin has been associated with decreased mortality and age-associated diseases [In summary, systemic administration of Metformin in vivo provided an effective preventive effect on the pathogenesis of the periodontal disease establishment and progression by controlling systemic and periodontal metabolism, reaction to oxidative damage, and inflammation. Moreover, within the limitations of our pilot trial, Metformin appears to be a useful novel therapeutic adjunct option to periodontal treatment management, however, further testing with dose titration in larger trials are needed. The safety, readiness, and cost-effectiveness of this approach makes Metformin an ideal translational approach that could potentially be adopted on a global scale.