Use of adjuncts in periodontal treatment for patients with diabetes

Background + Aims

• Diabetes mellitus (DM) is a common condition linked to systemic and oral complications, including periodontitis, with evidence of a bidirectional relationship between the two.
• Periodontal inflammation can worsen glycemic control, and adjunctive antimicrobial therapies may improve outcomes in diabetic patients undergoing scaling and root planing (SRP)
• Doxycycline at antimicrobial and sub-antimicrobial doses has been researched significantly and shown promise. The combination of metronidazole (MTZ) and amoxicillin (AMX) is recognized as effective in treating periodontitis in smoking and non-smoking patients. However, it remains untested in diabetic populations.
• This randomised clinical trial (RCT) aims to evaluate the clinical and microbiological effects of MTZ and AMX as adjuncts to SRP in patients with generalized chronic periodontitis (generalized ChP) and type 2 diabetes mellitus (T2DM).

Materials + Methods

• The sample size was calculated to detect a difference of ≥4 residual pockets with probing depth (PD) ≥5 mm between groups, with a standard deviation of five sites. To achieve 80% power at a 0.05 significance level, 24 subjects per group were needed. Accounting for a 15% attrition rate, the target was set at 29 subjects per group.
• Inclusion criteria:
  • Participants were ≥35 years old with T2DM for ≥5 years
  • HbA1c levels between 6.5% and 11%
  • ≥ 15 teeth (excluding third molars and severely decayed teeth).
  • >30% of sites with probing depth (PD) and clinical attachment level (CAL) ≥4 mm
  • ≥6 teeth with PD and CAL ≥5 mm and bleeding on probing (BOP)
• Exclusion criteria:
  • Participants who were pregnant, lactating, current or recent smokers, had recent periodontal or antimicrobial therapy, systemic conditions (other than diabetes) affecting periodontitis, long-term anti-inflammatory or immunosuppressive medication use, allergies to MTZ/AMX, orthodontic appliances, extensive prosthetic work, or severe diabetic complications (e.g., neuropathy, nephropathy, or vascular disease).
• A total of 58 participants were randomised into 2 groups:
  • Control: SRP + placebo pills for 14 days (n=29)
  • Test: SRP + MTZ (400 mg 3 times/ day) + AMX (500 mg 3 times/ day) for 14 days (n=29).
• The trial was double-blinded with allocation concealment
• Non-surgical periodontal treatment (NSPT) included:
  • Supragingival plaque and calculus removal
  • Oral hygiene instructions (OHI)
  • SRP in 4-6 sessions (approximately 1-hour per session)
  • Antibiotics/placebos were administered after the first session of SRP
• Supportive therapy was performed at 3-, 6- and 9-month post-SRP
• Clinical parameters such as PD, BOP, CAL, were assessed at six sites per tooth at baseline, 3-, 6-, and 12-months.
• Microbiological monitoring using qPCR was performed on subgingival biofilm samples at baseline, 3- and 12-months.
• Fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) levels were also measured at baseline, 3-, 6-, and 12-months.
• Outcomes analysed:
  • Primary:
    • Between-group difference in mean number of sites with PD ≥5 mm after treatment.
  • Secondary:
    • Between-group difference in risk classification for disease progression
    • Changes in PD and CAL at moderate and deep sites
    • Full-mouth PD, CAL, plaque levels, marginal bleeding, BOP, suppuration
    • Glycaemic parameters (HbA1c and FBG)
    • Changes in bacterial species
    • Adverse events.
• A variety of statistical analyses were conducted. Statistical significance was set at p<0.05.
  • The data were analysed on an intention-to-treat basis, carrying the last observation forward when necessary.

Results

• The study included 58 participants (38–65 years old), with 27 subjects in the control (SRP + placebo) and 29 subjects in the test (SRP + MTZ+AMX) group. 6 subjects were lost during follow-up (4 control, 2 test).
• Compliance with medication was high, with minor adverse effects reported in 6 control and 14 test subjects, but no significant differences between groups.
• Clinical outcomes:
  • Both groups showed significant clinical improvements at 3-, 6-, and 12-months post-treatment.
  • The test group demonstrated greater reductions in PD,greater CAL gains, and and fewer sites with PD ≥5 mm or ≥6 mm compared to the control group (p<0.05).
  • At 1 year, 75.9% of test group subjects were classified as “low risk” for disease progression, compared to 22.2% in the control group (p<0.05).
• Microbiological outcomes:
  • Both therapies reduced bacterial levels, but the test group achieved significantly lower levels of red complex bacteria (T. denticola, P. gingivalis, T. forsythia) and intermedia at 3- and 12-months (p<0.05).
  • The test group also showed greater reductions in nodatum at 3 months.
• Glycaemic outcomes:
  • There were no significant changes in HbA1c or FPG levels between or within groups.
  • No differences were observed in glycemic control, regardless of treatment.

Limitations