Bone tissue is well-known for its robust regenerative capacity(Ansari, 2019). However, in large defects caused by trauma, tumor resection, congenital anomalies, or systemic disease, this regenerative capacity may be insufficient(Matos et al., 2008). In clinical practice, one of the most common methods for treating such defects is the use of bone grafts (Fernandez de Grado et al., 2018). Bone grafts (autogenous graft, allograft, xenograft). from various sources aid healing by providing osteogenic cells, osteoinductive signals, and an osteoconductive scaffold (Ferraz, 2023). However, each graft type has its advantages and limitations, which have motivated the use of adjuvant biological or pharmacological agents to improve graft success (Lobb et al., 2019)

Recently, the effects of incretin-based treatment approaches on bone metabolism have gained significant attention in research (Papazafiropoulou et al., 2014). Liraglutide is a glucagon-like peptide-1 (GLP-1). receptor agonist used for type 2 diabetes (Madsbad et al., 2004). Liraglutide is a long-acting GLP-1 receptor agonist with a systemic bioavailability of approximately 55 % after subcutaneous injection (Knudsen et al., 2000). Although primarily known for its glucose-lowering effect via stimulation of pancreatic β-cells, GLP-1 receptors are widely expressed in extra-pancreatic tissues such as the heart, liver, kidneys, and central nervous system (Davies et al., 2018 Seino & Yabe, 2013). Consequently, Liraglutide exerts several pleiotropic effects, including anti-inflammatory, cardioprotective, and anabolic actions in peripheral organs (Lee & Jun, 2016). In addition to its metabolic effects, Liraglutide has been reported to exert systemic anti-inflammatory and tissue-protective properties, which may indirectly contribute to bone remodeling processes. Preclinical studies suggest that it positively influences bone formation and resorption, in addition to its effects on glycemic Control (Madsbad et al., 2004 Wu et al., 2017). Notably, osteoblasts and osteoclasts express GLP-1 receptors, so GLP-1 agonists, such as Liraglutide, could influence bone remodeling by altering cell growth, differentiation, and inflammatory responses (Papazafiropoulou et al., 2014)

However, the existing literature on the effects of Liraglutide on bone regeneration is generally limited to osteoporotic or diabetic animal models, and data on its use in combination with different graft materials are quite insufficient (Ahmad et al., 2025). However, the effects of this approach on bone healing when combined with different types of graft remain unclear. Therefore, in this study, we evaluated the impact of Liraglutide on bone regeneration when combined with autogenous graft, allograft, or xenograft materials, using a comprehensive set of outcome measures. We hypothesized that Liraglutide would enhance bone regeneration and modulate osteogenic marker expression when combined with different graft materials.