The primary search resulted in 17 articles but only 6 studies met the inclusion criteria, including 2 animal studies and 4 human trials. The studies showed that metformin administered intraperitoneally or intramuscularly in animal models reduced bone loss and increased bone formation. In human studies, the use of 1% metformin gel as an adjunct to scaling and root planning or open-flap debridement resulted in better clinical and radiographic outcomes compared to those treatments alone. A meta-analysis of the 6 studies found that the combination of metformin and periodontal therapy led to greater reductions in intrabony defect depth and increases in intrabony defect fill compared to periodontal therapy alone.

2. Resutls
The primary search resulted in 17 articles in total, after exclusion six studies were
included in this review. Two studies were animal studies and the the remaining
four were human trials

4. General background:
Addressed problem by the study
Periodontitis is characterized by inflammation of the periodontium and leads to loss of teeth if untreated.
Although a number of surgical and pharmacological options are available for the management of peri-
odontitis, it still affects a large proportion of population
Recently, metformin (MF), an oral hypoglycemic, has been used to treat periodontitis.

5. o Why is this important to the audience
Periodontitis, the inflammation of the periodontium, affects 40– 90% of the global population
Periodontitis is characterized by the progressive destruction of cementum, peri- odontal ligament and
alveolar bone and subsequently, loss of teeth
It has:
Local factors such as poor oral hygiene and use of tobacco
Systemic conditions such as malnutrition , diabetes, cardiovascular disease, infections and pregnancy
may also lead to manifestation of periodontitis.

6. Experimental and biological background
Lack of oral hygiene leads in the formation of dental plaque, a biofilm containing bacteria, lymphocytes,
neutrophils, Streptococcus intermedius and Treponema denticola are the major bacteria that have been
implicated in periodontitis.
The presence of bacteria leads to an exaggerated immune response which leads to destruction of
periodontal tissues.
Management of chronic periodontitis mainly involves the removal of the causative factors and to repair,
regenerate and maintain periodontal tissues .

7. Studies have also shown favorable effect of MF on bone formation. There are two mechanisms of action that
have been suggested for the osteogenic effect of MF: increased proliferation of osteoblasts and reduction of
osteoclast activity.
Thereby inducing bone formation and inhibiting bone resorption. More recently, MF has been used as an adjunct
to surgical and non-surgical periodontal therapy to treat chronic periodontitis.

8. Limitations and conclusion:
The patients were followed-up for no more than 9 months Therefore, the long-term efficacy of MF
in improving the outcomes of periodontal disease is unknown. there is risk of bias in the RCTs and
long-term efficacy of metformin.
. none of studies included histological analysis or bacterial studies which are crucial for accurate
assessment of attachment loss. Hence, it is unknown what effect MF has on human periodontal
tissues at the microscopic level and on the bacterial flora of the periodontal pockets.
only one study included smokers and none of the studies included diabetic patients. Hence, studies
focusing on the long- term outcome of MF on smokers and diabetic patients need to be conducted.

9. Continued-
Moreover Metformin is an effective medicament in improving the out- comes of surgical and non-
surgical periodontal therapy.
Especially that MF and PRF are more effective in improving outcomes when placed in intrabony
defects following OFD than PFD, PRF or MF alone, suggesting esting that MF may augment the
effect of PRF.
It is known that smoking has an adverse effect on periodontal health. Based on the results
obtained in the study by Rao et al., MF may prove to be a potent drug for improving outcomes
following SRP in smokers.

10. Results
-3 -2 -1 0 1 2 3
SRP
Only
better
Combination
therapy
?

11. Animal studies
• A total of 6 studies including animal and human studies were evaluated; the MF was intentionally deposited
intraperitoneally into the periapical area (10mg/kg) and intra-mauscular (40mg/kg) in animal studies groups. However, in
Human studies, the MF gel was prescibed with different doses (0.5-1.5%) depening on age (25-50).
• Intraperitoneally injections of MF in doses of 10mg/kg body weight resulted in a significantly higher number of osteoblasts
and reduced bone loss but did not have significant effect on the number of adipocytes and osteoclasts.
• IM injections of MF in doses of 40 mg/kg body weight resulted in lower RANKL/ OPG ratios and reduced number of
osteoclasts in addition to diminished bone loss

12. Human studies
• The use of 1% MF combined with scaling and root planning, or open-flap debridement showed better results clinically and
radiographically, compared with SRP and OPF alone.
• In term of MF dose, 1%MF combined with SRP showed better significant results compared to 0.5 and 1.5 % of MF.
• open-flap debridement, platelet-rich fibrin and 1% MF resulted in significantly higher improvement in parameters than
doing PRF + OFD or combining 1%MF and open-flap debridement

13. Meta-analysis
• Depending on the assessed parameter SRP + 1% MF resulted in significantly better results.
• However, in all 6 studies, the application of MF to surgical or non-surgical periodontal therapy resulted in better results of
IBD depth and IBD fill. The best improvement was measured as 2.7mm for IBD depth and 52.6% for IBD fill.