Liraglutide mitigates diabetic periodontitis and peri-implantitis in mice by controlling hyperglycemia, inflammation, and oral microbiota

Diabetic periodontitis (DP) and peri-implantitis are prevalent and challenging clinical conditions, often exacerbated by uncontrolled diabetes. Current treatments for these oral inflammatory diseases have limited efficacy, particularly in diabetic patients where hyperglycemia drives immune dysregulation, including excessive neutrophil extracellular trap (NET) formation. The bidirectional link between diabetes and periodontitis highlights the need for therapies that address both systemic metabolic dysfunction and local oral inflammation. GLP-1 receptor agonists (GLP-1RAs) like Liraglutide are known to interact with pathways involved in systemic low-grade inflammation, oxidative stress, and bone metabolism, making them potential candidates for addressing the complex pathogenesis of these conditions.

Researchers investigated the effects of Liraglutide and Indomethacin on experimental periodontitis and peri-implantitis in diabetic db/db mice. After implant placement, mice were subjected to ligature-induced periodontitis/peri-implantitis and treated with Liraglutide, Indomethacin, or both. The study assessed primary endpoints including bone loss, immune cell infiltration, inflammatory cytokine expression, osteoclast activity, RAGE expression, IL-17A-associated responses, and Foxp3+ Treg infiltration. Oral microbiota composition was analyzed using metagenomics and tested in vitro for inflammatory cytokine induction.

Liraglutide treatment, unlike Indomethacin, effectively reduced bone loss and immune cell infiltration in both periodontitis and peri-implantitis sites. It also significantly decreased RAGE and IL-17A expression while restoring the presence of Foxp3+ Treg cells. The oral microbiota composition in diabetic mice differed significantly from normoglycemic controls, exhibiting a pro-inflammatory profile. Liraglutide treatment produced the greatest deviation from the ligation-only profile, shifting the microbiome composition toward that of normoglycemic control mice. While local inflammatory responses and microbial alterations were similar between tooth and implant sites, peri-implant microbiomes demonstrated greater resistance to interventions. Furthermore, hyperglycemia control alleviated microbiome-induced pro-inflammatory responses in vitro.

Diabetic hyperglycemia was identified as a more predominant driver than systemic inflammation in exacerbating tissue destruction, immune dysregulation, and eliciting a pro-inflammatory oral microbial environment in these models.