Incretin-Based Antidiabetic Therapies and Orthodontic Tooth Movement: Biological Mechanisms, Evidence, and Clinical Implications

Abstract

Background

The increasing prevalence of type 2 diabetes mellitus and obesity has resulted in a growing number of orthodontic patients receiving incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs) and glucose-dependent insulinotropic polypeptide (GIP)-related agents. Beyond glycemic control, these medications regulate bone remodeling, inflammatory signaling, and osteoclast–osteoblast interactions, raising important questions regarding their influence on orthodontic tooth movement (OTM).^(1-4)

Objective

To summarize current evidence regarding the effects of incretin-based antidiabetic therapies on bone remodeling during orthodontic tooth movement and discuss their potential clinical implications for orthodontic treatment.

Methods

A comprehensive literature review was conducted using experimental studies, clinical investigations, systematic reviews, and mechanistic reviews evaluating GLP-1 receptor agonists, GIP signaling, bone metabolism, osteoclastogenesis, and orthodontic tooth movement. Evidence was synthesized to describe biological mechanisms, experimental findings, and current clinical relevance.

Results

Available evidence indicates that incretin signaling modulates bone remodeling by suppressing inflammatory cytokines, reducing RANKL-mediated osteoclast differentiation, promoting osteoblast activity, and improving bone quality. Experimental orthodontic studies consistently demonstrate that GLP-1 receptor agonists decrease osteoclastogenesis, reduce alveolar bone resorption, slow orthodontic tooth movement, and diminish orthodontically induced inflammatory root resorption. Similar findings have been reported for GIP signaling, suggesting a regulatory role in force-induced bone remodeling. However, nearly all orthodontic evidence originates from animal models, while clinical studies in orthodontic patients remain unavailable.^(2-8)

Conclusions

Incretin-based therapies appear to influence orthodontic tooth movement through modulation of bone remodeling and inflammatory pathways. Although current preclinical evidence suggests reduced tooth movement and potential protection against root resorption, the absence of prospective human studies limits clinical translation. Well-designed clinical investigations are required before orthodontic treatment protocols can be modified for patients receiving these medications.^(5-8)