Periodontal disease is a complex inflammatory condition associated with an imbalance in the microbial environment, requiring effective cell turnover and regulation of inflammation to counter the ongoing bacterial attack on the periodontium.1
Throughout a person’s life, the gingival tissues face constant bacterial challenges, and current methods for treating and preventing periodontal disease primarily focus on antimicrobial strategies, including the temporary removal of biofilm and the use of adjunctive antibiotic treatments.1
Although advances have been made in periodontal treatment over the years, gingivitis still affects 90% of the global population, and periodontitis remains the sixth most prevalent disease worldwide. Considering the widespread and preventable nature of this condition, there is a pressing need to develop more effective, user-friendly, and minimally invasive approaches to manage and control periodontal disease progression without relying solely on antimicrobial therapies.1
A recent study investigated the effect of Metformin, a medication used for glycemic control for those with type 2 diabetes, on acute systemic inflammation during periodontal treatment in patients without diabetes.1
The Study
Twenty patients in good health without a current or previous diagnosis of diabetes and diagnosed with generalized periodontitis at stage 3 or 4, grade B or C, were selected for a trial requiring non-surgical periodontal therapy. These participants were randomly divided into a control group (placebo, n = 10) and a test group (850 mg oral Metformin, n = 10).1
Participants were excluded from the study if they were currently undergoing cancer treatment, taking immunosuppressive medications, or had a history of alcohol or tobacco use. Additionally, those with renal failure, liver abnormalities, congestive heart failure, or a history of acute myocardial infarction within the past six months were not eligible.1
Individuals with respiratory conditions such as pneumonia, pulmonary embolism, asthma, or chronic obstructive pulmonary disease, as well as those with allergies to any component of the medication, were also excluded. Participants using medications that could interfere with the study protocol, such as anti-inflammatories or antibiotics, and those unwilling to sign the informed consent were excluded.1
Each participant was instructed to take one oral tablet daily in the morning with breakfast, starting three days before periodontal treatment. Baseline blood and gingival crevicular fluid samples were collected for laboratory analysis before treatment. On the third day of medication, participants received full mouth non-surgical periodontal therapy. During the procedure, granulation tissue from the deepest periodontal pocket was collected.1
After treatment, participants continued to take their assigned medication, once daily in the morning with breakfast, for an additional seven days, following a regimen like that of antibiotic therapy. Participants received either a placebo or 850 mg of Metformin for ten days.1
Results
Periodontitis and gingivitis are distinguished by the extent of damage they cause to the supporting periodontal tissues, with periodontitis resulting in irreversible destruction even after microbial challenges are addressed. The exact mechanisms that drive the transition from stable chronic gingivitis to destructive periodontitis remain uncertain.1
Biofilm accumulation, an everyday physiological occurrence, influences the inflammatory response of gingival tissues. Additionally, glycemia is another physiological factor that impacts the progression of diseases with inflammatory risk factors like periodontal disease.1
Although Metformin is not commonly used in dental practice, this in vivo research demonstrates that its systemic use effectively maintains stable glucose levels and influences cellular energy metabolism and differentiation in gingival epithelial and stromal cells. This has been shown to enhance the prevention of periodontal disease onset, even amidst dysbiosis.1
Testing an in vivo model of bacteria-induced gingival inflammation in human patients would be unethical, mainly since systemic Metformin has not been used in periodontal disease management before. To address this gap, the authors conducted a trial to explore the potential of systemic Metformin as an adjunctive treatment for periodontal disease.1
The study found that Metformin helps control systemic and local inflammatory responses post-treatment, leading to modest improvements in clinical periodontal parameters. Although the study had a small sample size (which limited its statistical power) and the medication was administered for only ten days, the results were promising, suggesting that Metformin could be beneficial as an adjunct to periodontal treatment.1
An essential aspect of the trial was the dosage of Metformin. For previous animal studies, a dose of 1200 mg per day was utilized, which is optimal for diabetes management and has been associated with increased longevity.1
In contrast, patients in the current trial without diabetes received a lower dose of 850 mg per day, which is a lower dose than the typical dosage for diabetes management. Given the variability of biofilm and glucose levels during treatment and the lower dose used, extending the duration of Metformin administration might lead to significantly improved periodontal outcomes.1
In comparison, systemic antibiotics used as adjuncts to periodontal treatment have been shown to improve periodontal pocket depths by 0.26 to 0.53 mm following subgingival instrumentation. In the current study, systemic Metformin at the given dosage improved periodontal pocket depths by 0.21 mm after 12 weeks. This suggests potential for optimizing both the dose and duration of Metformin treatment.1
Additionally, while patients receiving Metformin had more biofilm accumulation than those on placebo, they exhibited lower inflammation levels, as indicated by bleeding indices. They showed more significant pocket depth reduction and clinical attachment gains.1
In the current clinical study, systemic Metformin accelerated healing, as evidenced by a significant reduction in periodontal pocket depths at six weeks. This finding aligns with previous in vivo research highlighting Metformin’s ability to accelerate wound healing. The results suggest that Metformin’s effects in periodontal treatment likely involve modulation of inflammation with oxidative stress regulation.1
Additionally, on a systemic level, Metformin administered alongside periodontal treatment helped stabilize fasting glucose and high-sensitivity C-reactive protein levels while reducing insulin levels. These systemic changes have indirectly improved the local effects observed in biological and clinical parameters. Overall, Metformin could serve as a valuable adjunct in managing periodontal disease, potentially offering oral and systemic health benefits.1
Conclusion
In this pilot study, systemic administration of Metformin demonstrated a significant preventive effect against the development and progression of periodontal disease by managing systemic and periodontal metabolism, oxidative stress, and inflammation.1
Despite the limitations of this pilot study, Metformin shows promise as a novel adjunctive therapy for periodontal treatment. However, additional research with dose adjustments and larger sample sizes must confirm these findings. Given its safety, availability, and cost-effectiveness, Metformin presents a promising translational approach that could be implemented globally.1
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References
1. Neves, V.C.M., Satie Okajima, L., Elbahtety, E., et al. Repurposing Metformin for Periodontal Disease Management as a Form of Oral-Systemic Preventive Medicine. J Transl Med. 2023; 21(1): 655. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/37814261/
