Adjunctive melatonin in periodontal therapy for type 2 diabetic patients: Systematic review and Meta-Analysis

Melatonin has anti-inflammatory and antioxidant properties relevant to periodontal therapy. However, its effectiveness as an adjunct in patients with type 2 diabetes and periodontitis remains uncertain. This meta-analysis evaluated its clinical impact in this population.

We searched PubMed, Embase, and the Cochrane Library through June 2025 for studies comparing adjunctive melatonin plus scaling and root planing (SRP) versus SRP alone or placebo in patients with type 2 diabetes and periodontitis. Primary outcomes were probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP). Secondary outcome: plaque index (PI). Meta-analyses used a random-effects model (Review Manager 5.4), and risk of bias was assessed with the Cochrane RoB 2 tool.

Of 79 records, 4 studies (269 participants) were included. Adjunctive melatonin significantly improved PD (mean difference [MD]: -1.38 mm; 95% CI: -2.28 to - 0.47; p = 0.003) and CAL (MD: -1.17 mm; 95% CI: -1.82 to - 0.52; p = 0.0004). BOP also improved (risk ratio [RR]: 0.68; 95% CI: 0.53 to 0.88; p = 0.003). Sensitivity analyses excluding one outlier showed larger effects and reduced heterogeneity. PI data, descriptively analyzed, favored melatonin.

Adjunctive melatonin improves clinical periodontal parameters and reduces inflammation in patients with type 2 diabetes and periodontitis. These findings suggest melatonin may serve as a biologically plausible and well-tolerated adjunct, though current evidence remains limited and should be interpreted with caution. Further high-quality trials are needed to confirm these outcomes.