Sub-antimicrobial doxycycline for periodontitis reduces hemoglobin A1c in subjects with type 2 diabetes: A pilot study

In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation. We conducted a 3-month, randomized placebo-controlled pilot clinical trial of conventional sub-gingival debridement (periodontal therapy), combined with either a three month regimen of sub-antimicrobial-dose doxycycline (SDD), a two week regimen of antimicrobial-dose doxycycline (ADD), or placebo in 45 patients with long-standing type 2 diabetes (mean duration 9 years) and untreated chronic periodontitis. Subjects were taking stable doses of oral hypoglycemic medications and/or insulin. Treatment response was assessed by measuring hemoglobin A1c (HbA1c), plasma glucose, and clinical periodontal disease measures. At one-month and three-month follow-up, clinical measures of periodontitis were decreased in all groups (data to be presented elsewhere). At three months, mean HbA1c levels in the SDD group were reduced 0.9% units from 7.2% units ± 2.2 (±SD), to 6.3% units ± 1.1, which represents a 12.5% improvement. In contrast, there was no significant change in HbA1c in the ADD (7.5% ± 2.0 to 7.8% ± 2.1) or placebo (8.5% ± 2.0 to 8.5% ± 2.6) groups. Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group (p = 0.04) but not placebo (p = 0.22). Moreover, a larger proportion of subjects in the SDD group experienced improvement (p < 0.05) compared to the ADD or placebo groups. Mean plasma glucose levels were not significantly different between or within the groups. The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents.