Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Ameliorates the Development of Periodontitis

Abstract

Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague–Dawley (SD) rats ( n = 30 ) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.

Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis

“…Swada et al . recently revealed that liraglutide ameliorates the development of periodontitis, which was demonstrated by a decrease in periodontitis-induced inflammation, decrease in M1 macrophages in the gingiva, and alveolar bone loss with decreased osteoclast formation 51 . Moreover, Wan et al .…”

Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis

“…In the opposite direction, improving glucose control is beneficial in preventing both onset and progression of chronic complications of DM and this is also likely true for periodontitis. Moreover, recent studies in both experimental animals and humans suggest that drugs that are currently used for the treatment of DM2 have additional beneficial effects in periodontitis independently of their glucose-lowering action [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Local application of 1% metformin gel into the periodontal pockets improves periodontitis when given on the top of scaling and root planning [ 53 ].…”

“…Recent studies in experimental animals suggest that drugs that are currently used for the treatment of DM2, such as metformin, sulfonylureas, and GLP-1 receptor agonists, may also have direct beneficial effects in periodontitis by decreasing inflammation [ 48 , 51 , 52 ], bacterial dysbiosis [ 49 , 50 ], and bone loss and by enhancing bone formation [ 47 , 226 ]. This suggests that, beyond lowering blood glucose levels, anti-diabetic drug may also have pleiotropic effects of potential relevance in the context of periodontitis.…”

Next-Generation Examination, Diagnosis, and Personalized Medicine in Periodontal Disease

“…The hormone glucose-dependent insulinotropic polypeptide (GIP), which is elevated by dipeptidyl peptidase-4 (DPP-4) inhibitors (incretin-related drugs) for the treatment of type 2 diabetes, has been shown to suppress inflammation in experimental periodontitis [ 137 ]. In contrast, glucagon-like peptide-1 (GLP-1) receptor agonists, a treatment for type 2 diabetes, have been shown to reduce alveolar bone resorption caused by experimental periodontitis [ 138 ]. These have shown improvement in periodontal disease when diabetes drugs are acted on in models of periodontal disease alone, suggesting that they may directly cause improvement in the periodontal disease condition when used as a diabetes drug.…”