{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:34:29Z","timestamp":1792978469277,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty male Wistar rats (10\u201314 weeks old, 350 \u00b1 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 15<jats:sup>th<\/jats:sup>, 30<jats:sup>th<\/jats:sup>, and 45<jats:sup>th<\/jats:sup> days, four rats from each group were selected randomly and euthanized, and the femurs were examined radiographically, biomechanically, and histopathologically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The baseline characteristics of the rats before the study showed no significant differences between the groups (p&amp;gt;0.05). Biomechanical test results showed a significant main effect of group (p&amp;lt;0.001), indicating that overall Newton values varied across groups. Additionally, a significant main effect of experimental day was found (p&amp;lt;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 15<jats:sup>th<\/jats:sup> day (p=0.934), 30<jats:sup>th<\/jats:sup> day (p=0.649), and 45<jats:sup>th<\/jats:sup> day (p=0.502) of the experiment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1703958","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:13:08Z","timestamp":1761019988000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The effects of liraglutide and metformin treatment on fracture healing in partially insulinopenic diabetic 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