GLP-1受体激动剂在牙科中的应用：前景、陷阱与证据空白

文献信息

中文摘要

GLP-1RAs（胰高血糖素样肽-1受体激动剂）已成为全球增长最快的药物类别之一，2019年至2024年间用于肥胖治疗的处方量增加了587%。尽管其代谢和心血管获益已得到充分证实，但对口腔健康的影响仍基本未被研究。临床前证据一致表明其对牙周和种植体周围组织具有抗炎和骨保护作用：GLP-1RAs促进牙周膜干细胞的成骨分化，减少牙周炎动物模型中的牙槽骨吸收，并增强糖尿病大鼠的种植体骨整合。然而，这些发现完全基于体外和动物研究，仅有一项回顾性队列研究提供了有限的临床数据。相反，基于药物警戒分析已报告了若干口腔不良效应，包括口干症、味觉障碍和嗅觉丧失，尤其是司美格鲁肽。胃肠道副作用，特别是恶心（15%至50%）、呕吐（5%至24%）和胃食管反流，对牙齿侵蚀和继发龋构成合理但未量化的风险。GLP-1信号与口腔微生物群之间的双向联系，由降解内源性GLP-1的细菌二肽基肽酶（DPP）-4样酶介导，进一步增加了复杂性。尽管存在如此广泛的潜在相互作用，尚无前瞻性研究在接受GLP-1RAs的患者中以任何牙科结局作为终点。本批判性评估综合了多个牙科领域的证据，对每个领域进行分级，并确定了亟待调查的空白。

英文摘要

GLP-1RAs (glucagon-like peptide-1 receptor agonists) have become one of the fastest-growing drug classes worldwide, with prescriptions for obesity treatment increasing by 587% from 2019 to 2024. While their metabolic and cardiovascular benefits are well established, the implications for oral health remain largely unexamined. Preclinical evidence consistently demonstrates anti-inflammatory and osteoprotective effects on periodontal and peri-implant tissues: GLP-1RAs promote osteogenic differentiation of periodontal ligament stem cells, reduce alveolar bone resorption in animal models of periodontitis, and enhance implant osseointegration in diabetic rats. However, these findings are based exclusively on in vitro and animal studies, with only a single retrospective cohort study providing limited clinical data. Conversely, several oral adverse effects have been reported based on pharmacovigilance analyses, including xerostomia, dysgeusia, and anosmia, particularly for semaglutide. Gastrointestinal side effects, particularly nausea (15% to 50%), vomiting (5% to 24%), and gastroesophageal reflux, pose a plausible but unquantified risk for tooth erosion and secondary caries. A bidirectional link between GLP-1 signaling and the oral microbiota, mediated by bacterial dipeptidyl peptidase (DPP)-4-like enzymes that degrade endogenous GLP-1, adds further complexity. Despite this breadth of potential interactions, no prospective study has used any dental outcome as an endpoint in patients receiving GLP-1RAs. This critical appraisal synthesizes the evidence across multiple dental disciplines, grades it in each domain, and identifies the gaps that demand urgent investigation.