Sulfonylureas for Treatment of Periodontitis-Diabetes Comorbidity-Related Complications: Killing Two Birds With One Stone

Abstract

Periodontitis is one of the most prevalent oral inflammatory diseases leading to teeth loss and oral health problems in adults. Periodontitis mainly affects periodontal tissue by affecting the host immune system and bone homeostasis. Moreover, periodontitis is associated with various systemic diseases. Diabetes is a metabolic disease with systemic effects. Both periodontitis and diabetes are common inflammatory diseases, and comorbidity of two diseases is linked to exacerbation of the pathophysiology of both diseases. Since bacterial dysbiosis is mainly responsible for periodontitis, antibiotics are widely used drugs to treat periodontitis in clinics. However, the outcomes of antibiotic treatments in periodontitis are not satisfactory. Therefore, the application of anti-inflammatory drugs in combination with antibiotics could be a treatment option for periodontitis-diabetes comorbidity. Anti-diabetic drugs usually have anti-inflammatory properties and have shown beneficial effects on periodontitis. Sulfonylureas, insulin secretagogues, are the earliest and most widely used oral hypoglycemic drugs used for type-2 diabetes. Studies have found that sulfonylurea drugs can play a certain role in the mitigation of periodontitis and inflammation. This article reviews the effects of sulfonylurea drugs on the mitigation of periodontitis-diabetes comorbidity-related inflammation, bone loss, and vascular growth as well as the involved molecular mechanisms. We discuss the possibility of a new application of sulfonylureas (old drug) to treat periodontitis-diabetes comorbidity.

Developmental endothelial locus‐1 promotes osteogenic differentiation and alveolar bone regeneration in experimental periodontitis with type 2 diabetes mellitus

“…21 It is believed that periodontitis and diabetes are related in a bidirectional manner. 22,23 Treatment modalities for periodontitis with T2DM are being explored. It is realized that effectively promoting alveolar bone regeneration in the inflammation resolution stage may provide a new perspective on periodontitis with T2DM treatment.…”

“…Periodontitis is an inflammatory disease that leads to inflammatory bone loss around teeth 21 . It is believed that periodontitis and diabetes are related in a bidirectional manner 22,23 . Treatment modalities for periodontitis with T2DM are being explored.…”

Effect of incretins on skeletal health

“…Another animal study using Zucker diabetic fatty rats report that GLP-1 RA promote osteoblastogenesis by attenuating the effect of advanced glycation endproducts (AGEs), oxidative stress and suppress bone resorption. A model of diabetic periodontitis in male Wistar rats report that administration of GLP-1 RA compared to saline increased BMD, trabecular thickness, trabecular number, and cortical thickness [27]. To illustrate the controversy of the evidence from animal studies on incretins and skeletal effects, a male Wistar rat model showed that treatment with a GLP-1 RA or a DPP4-i, which inhibits degradation of the GLP-1 molecule, reduced osteoclast function but could not revert osteoblast function and the impairment of bone strength in the diabetic state compared to controls [28].…”

“…Increase osteoblastogenesis, osteoblastic differentiation and bone formation [22,25,27] and may alleviate negative effects from hyperglycemia [23] May not be translated to humans fractures. This balance is illustrated in Fig.…”

Therapeutic Potential of Liraglutide for Diabetes–Periodontitis Comorbidity: Killing Two Birds with One Stone

“…The results showed that insulin could improve inflammatory cell infiltration and expression of inflammatory cytokine genes and reduced the loss of alveolar bone. In addition, sulfonylurea drugs alleviate periodontitis possibly via direct mitigation of inflammation or indirectly via an antidiabetic effect [ 11 ]. Our previous experiments have also shown that hypoglycemic drug liraglutide (LIRA) can promote osteogenesis and inhibit the inflammatory reaction of human periodontal ligament cells (hPDLCs) stimulated by lipopolysaccharide, and confirm the therapeutic effect of LIRA on periodontitis in rats [ 12 , 13 ].…”