M Chavez ¹ A Ramirez ¹ Akram Hernández-Vásquez ² D Comandé ³ Diego Azañedo ^1*

• ¹ Scientific University of the South, Villa EL Salvador, Peru
• ² Center of Excellence in Health Economic and Social Research, Vice Rectorate for Research, San Ignacio de Loyola University, Lima, Peru., Lima, Peru
• ³ Institute for Clinical Efectiveness and Health Policy (IECS), Buenos Aires, Buenos Aires, Argentina

Introduction: This study synthesizes evidence on the impact of subgingival periodontal treatment combined with antibiotics on reducing systemic inflammation markers—C-reactive protein (CRP), interleukins, and tumor necrosis factor-alpha (TNF-α)—in patients with metabolic syndrome (MS) and periodontal disease (PD), compared to supragingival periodontal treatment with placebo. Methods: Randomized clinical trials (RCTs) published in English, Spanish, or Portuguese that addressed the research question were included. A search was conducted in eight databases (PubMed, EMBASE, CINAHL, LILACS, Scopus, WoS Core Collection, Dentistry & Oral Science Source, and Cochrane Central) on June 20, 2023. Risk of bias was assessed using the Cochrane RoB 2 tool, and evidence certainty was evaluated following GRADE guidelines. A qualitative synthesis of the evidence was performed. Results: Two RCTs with 228 participants (ages 35–65) were included. Montero et al. reported significant reductions in CRP levels favoring the treatment group at 3 months (2.7 mg/L ± SE: 0.4 vs. 3.9 mg/L ± SE: 0.6; p=0.001) and 6 months (2.9 mg/L ± SE: 0.4 vs. 4.0 mg/L ± SE: 0.8; p=0.004). Lopez et al., however, found no significant differences throughout follow-up. Only Montero et al. reported on interleukin 1β and TNF-α, observing significant reductions at 3 months for interleukin 1β (0.9 pg/dL ± SE: 0.1 vs. 2.3 pg/dL ± SE: 0.5; p=0.046) and TNF-α (6.4 pg/dL ± SE: 0.8 vs. 10.0 pg/dL ± SE: 2.3; p=0.037). Discussion: The evidence is limited by the small number of comparative RCTs. One RCT with low risk of bias demonstrated significant reductions in CRP, interleukins, and TNF-α levels at 3 months and CRP at 6 months. The other, with unclear risk of bias, showed no differences in CRP up to 12 months. Findings suggest that subgingival periodontal treatment with antibiotics reduces systemic inflammation for up to 6 months in patients with MS and PD. However, larger RCTs with standardized methods and longer follow-up are needed to confirm these results. Funding: The Scientific University of the South partially funded this project and will contribute to the journal's APC payment. Registration: The search protocol was registered in PROSPERO (CRD42022366056).