Semaglutide reduces spinal implant infection and improves wound healing in murine Type 1 and Type 2 diabetes

Spinal surgery carries a significant risk of postoperative infection and wound complications, particularly in patients with diabetes mellitus (DM). Current standard-of-care often focuses on glycemic control, but the distinct pathophysiological contributions of Type 1 (T1DM) and Type 2 (T2DM) diabetes to infection susceptibility are rarely differentiated. This gap highlights the need for targeted therapies that address the specific immune dysregulation in each diabetic phenotype, potentially improving surgical outcomes beyond traditional approaches.

Male C57BL/6J mice were used to model diabetes: T1DM was induced by streptozotocin, while T2DM was induced by a high-fat, high-sucrose diet. Spinal implants were surgically placed and then inoculated with bioluminescent Staphylococcus aureus to establish infection. Infection progression was tracked longitudinally using in vivo bioluminescence imaging. Systemic inflammation was characterized via multiplex cytokine profiling, and paraspinal tissues were analyzed post-mortem using histology and multiplex immunofluorescence. Diabetic cohorts received metabolic intervention with semaglutide (dose not specified in abstract) to assess therapeutic response.

Both diabetic models consistently demonstrated greater infection burden and delayed wound healing compared to nondiabetic controls. Distinct inflammatory profiles emerged: T2DM was characterized by chronically elevated baseline inflammation and a blunted acute response to infection, whereas T1DM exhibited low baseline activity but an exaggerated and dysregulated cytokine induction post-infection. Treatment with semaglutide significantly:

attenuated infection severity, improved wound integrity, and partially normalized inflammatory patterns. Histology and immunofluorescence further corroborated these findings, revealing reduced immune cell infiltration and improved tissue organization in the semaglutide-treated cohorts, indicating a restoration of immune balance and enhanced tissue repair.