| Summary: | <i>Background and Objectives</i>: There is evidence that melatonin could improve the periodontal status and also glycemic control of patients with diabetes mellitus. Therefore, the aim of this study was to assess the effects of scaling and root planing plus adjunctive systemic treatment with melatonin on periodontal parameters and glycemic control in patients with type 2 diabetes and chronic periodontitis. <i>Materials and Methods</i>: The study was conducted on 54 subjects with periodontitis and diabetes mellitus randomly assigned to the study group (<i>n</i> = 27, subjects with scaling and root planing + melatonin) or control group (<i>n</i> = 27, subjects with scaling and root planing + placebo). Periodontal parameters (probing depth—PD; clinical attachment loss—CAL; bleeding on probing—BOP; and hygiene level) and glycated hemoglobin (HbA1c) were assessed at baseline and 8 weeks after. <i>Results</i>: At baseline, there were no significant differences between groups, but at the second evaluation 8 weeks later the association of melatonin with the non-surgical periodontal therapy exerted statistically significant improvements, both in periodontal parameters, with a significant decrease in periodontal disease severity, and glycated hemoglobin when compared to the control subjects. <i>Conclusions</i>: In our study, combined non-surgical periodontal treatment and systemic treatment with melatonin provided additional improvements to severe periodontal condition and the glycemic control of patients with diabetes type 2 when compared to non-surgical periodontal treatment alone.
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