Ahmad Paras, Estrin Nathan, Farshidfar Nima, Zhang Yufeng, Miron Richard J
Department of Research, Advanced PRF Education, Florida, USA.
Lake Erie College of Osteopathic Medicine School of Dental Medicine, Bradenton, Florida, USA.
J Periodontal Res. 2025 May;60(5):450-465. doi: 10.1111/jre.13410. Epub 2025 May 9.
Type 2 diabetes mellitus (T2DM) affects millions globally and is strongly associated with oral health issues, particularly periodontitis. The bidirectional relationship between T2DM and periodontitis is well established, with poorly managed T2DM increasing the risk of inflammation, tissue damage, and dental implant failure. Advances in treatment, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), have led to better glycemic control and may reduce T2DM-related complications, highlighting their potential in addressing interconnected oral-systemic health challenges. This narrative review critically evaluates the literature on the impact of GLP-1RAs on periodontal and peri-implant health. 10 in vitro studies, nine preclinical animal studies, and one clinical study were explored to investigate their effects on periodontal regeneration, implant therapy, and related mechanisms. In vitro research revealed that GLP-1RAs, including exenatide and liraglutide, promoted osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through pathways such as the mitogen Wnt/β-catenin and mitogen-activated protein kinase pathways, even in high glucose or inflammatory conditions. Synergistic effects with stromal cell-derived factor-1 further promoted PDLSC proliferation and bone regeneration. Animal studies demonstrated that GLP-1RAs mitigated periodontal inflammation, oxidative stress, and alveolar bone resorption while promoting bone remodeling and implant osseointegration, independently of glycemic control. Importantly, advanced delivery systems, such as exenatide-loaded chitosan-poly(lactic-coglycolic acid) microspheres, further increased peri-implant osseointegration in diabetic models. The sole clinical study, a retrospective cohort study, assessed peri-implant marginal bone loss in peri-implantitis patients treated with different hypoglycemic drugs. Results showed significantly less clinical and radiographic bone loss in the GLP-1RA group compared to insulin and metformin groups (p < 0.01). Overall, while GLP-1RAs have promising anti-inflammatory, osteoprotective, and pleiotropic properties, their role appears more aligned with preserving periodontal and peri-implant health in T2DM individuals than directly treating periodontitis or peri-implantitis. By delineating current evidence and research directions, this review calls for medical and dental professionals to collaborate in leveraging these novel treatment options in future studies to improve patient care and address the intricate challenges that diabetes presents to oral health.
2型糖尿病（T2DM）在全球影响着数百万人，并且与口腔健康问题密切相关，尤其是牙周炎。T2DM与牙周炎之间的双向关系已得到充分证实，T2DM管理不善会增加炎症、组织损伤和牙种植体失败的风险。治疗方面的进展，如胰高血糖素样肽1受体激动剂（GLP-1RAs），已带来更好的血糖控制，并可能减少T2DM相关并发症，凸显了它们在应对相互关联的口腔-全身健康挑战方面的潜力。本叙述性综述批判性地评估了关于GLP-1RAs对牙周和种植体周围健康影响的文献。我们检索了10项体外研究、9项临床前动物研究和1项临床研究，以调查它们对牙周再生、种植治疗及相关机制的影响。体外研究表明，包括艾塞那肽和利拉鲁肽在内的GLP-1RAs，即使在高血糖或炎症条件下，也能通过丝裂原Wnt/β-连环蛋白和丝裂原活化蛋白激酶等途径促进牙周膜干细胞（PDLSCs）的成骨分化。与基质细胞衍生因子-1的协同作用进一步促进了PDLSC的增殖和骨再生。动物研究表明，GLP-1RAs可减轻牙周炎症、氧化应激和牙槽骨吸收，同时促进骨重塑和种植体骨整合，且与血糖控制无关。重要的是，先进的给药系统，如载有艾塞那肽的壳聚糖-聚（乳酸-乙醇酸）微球，进一步增加了糖尿病模型中种植体周围的骨整合。唯一的临床研究是一项回顾性队列研究，评估了接受不同降糖药物治疗的种植体周围炎患者的种植体周围边缘骨丢失情况。结果显示，与胰岛素和二甲双胍组相比，GLP-1RA组的临床和影像学骨丢失明显更少（p<0.01）。总体而言，虽然GLP-1RAs具有有前景的抗炎、骨保护和多效性特性，但它们的作用似乎更在于保护T2DM患者的牙周和种植体周围健康，而非直接治疗牙周炎或种植体周围炎。通过阐述当前的证据和研究方向，本综述呼吁医学和牙科专业人员在未来研究中合作利用这些新的治疗选择，以改善患者护理，并应对糖尿病给口腔健康带来的复杂挑战。
