The Effects of Liraglutide and Metformin Treatment on Fracture Healing in Partially Insulinopenic Diabetic Rats

Banu Turhan^1*Sönmez Sağlam²Mücahid Osman Yücel²Raşit Emin Dalaslan²Mehmet Ali Sungur³Fatih Demir⁴Zekeriya Okan Karaduman²Mehmet Arıcan²

• ¹Department of Pediatric Endocrinology, Ankara Ataturk Sanatoryum Egitim ve Arastirma Hastanesi, Ankara, Türkiye
• ²Department of Orthopaedics and Traumatology, Duzce Universitesi Tip Fakultesi, Düzce, Türkiye
• ³Department of Biostatistics and Medical Informatics, Duzce Universitesi Tip Fakultesi, Düzce, Türkiye
• ⁴Department of Pathology, Duzce Universitesi Tip Fakultesi, Düzce, Türkiye

Purpose: Although Metformin has been studied, the comparative or synergistic effect with GLP-1 agonists like Liraglutide on fracture healing remains poorly characterized. This study aimed to evaluate the impact of metformin, liraglutide, and their combination on fracture healing in a rat model of partially insulinopenic diabetes mellitus (DM). Methods: Sixty male Wistar rats (10-14 weeks old, 350±50g) were divided into five groups of twelve rats each: Control, DM, Met (Metformin), L (Liraglutide), and Met+L. Partially insulinopenic DM was induced in all experimental rats except the control group using streptozotocin (STZ) and nicotinamide (NA) combination. A femoral fracture was created, and a Kirschner wire was inserted retrogradely into the femoral canal. Liraglutide was injected subcutaneously at a daily dose of 0.6 mg/kg into the rats in the L and Met+L groups, and oral metformin was administered to the rats in the Met and Met+L groups daily at a dose of 180 mg/kg. On the 15th, 30th, and 45th days, four rats from each group were selected randomly and euthanized, and the femurs were examined radiographically, biomechanically, and histopathologically. Results: The baseline characteristics of the rats before the study showed no significant differences between the groups (p>0.05). Biomechanical test results showed a significant main effect of group (p<0.001), indicating that overall Newton values varied across groups. Additionally, a significant main effect of experimental day was found (p<0.001), suggesting that Newton values changed across days regardless of group. Histopathological scores showed a statistically significant difference between the groups on the 15th day, with the L group having 75% scoring 7 (p=0.047), and on the 45th day, with the L and Met+L groups both having 75% scoring 9 (p=0.036). Conversely, no significant difference was found in radiological scores between the groups on the 15th day (p=0.934), 30th day (p=0.649), and 45th day (p=0.502) of the experiment. Conclusion: Both metformin and liraglutide improve fracture healing in a partially insulinopenic diabetic rat model, and these findings suggest that liraglutide may offer a superior therapeutic advantage over metformin in accelerating fracture repair in patients with diabetes.