GLP-1 Agonists and Orthopedic Surgery: A Review of Their Impact on Bone Metabolism, Wound Healing, and Surgical Outcomes

Background The use of glucagon-like peptide-1 receptor agonists (GLP-1s) has surged in response to the growing prevalence of type 2 diabetes mellitus and obesity—two conditions that are known to elevate the risk of perioperative complications in orthopedic surgery. Despite the widespread adoption of GLP-1s, limited research exists examining their implications within the field of orthopedics. This review aims to evaluate the current evidence on GLP-1s as it relates to bone metabolism, wound healing, and surgical outcomes, with the goal of informing clinical decision-making and guiding future research in orthopedic surgical care. Methods A comprehensive literature review of PubMed, Embase, and Elsevier databases identified 17 relevant studies published between 2013 and 2024 that investigated the role of GLP-1 receptor agonists in bone metabolism, wound healing, and orthopedic surgery. Studies published before 2013, non-English language articles, and case reports were excluded. Given the heterogeneity of study designs and outcomes, results were synthesized using a narrative approach. Results Bone metabolism: Five preclinical studies found GLP-1 agonists enhanced osteoblastic differentiation and increased bone formation in osteoporotic and diabetic models. Four literature reviews concluded GLP-1s increased bone formation, three of which found them superior to other diabetes medications. Two randomized control clinical trials reported conflicting effects on bone mineral content (BMC) and bone mineral density (BMD): one trial demonstrated preservation of BMC with GLP-1 use, while the other found no significant difference in BMC or BMD between treatment and control groups. Wound healing: Three studies associated GLP-1s with reduced all-cause mortality. Two studies reported a significant reduction in lower limb amputations (LLA) and diabetic foot ulcers, while one study found no significant difference in LLA compared to other diabetic therapies. Surgical outcomes: A preclinical model found a 47% reduction in periprosthetic joint infections with GLP-s compared to insulin and a 61% reduction compared to untreated diabetic controls. Additionally, reactive oxygen species production increased by 22% and neutrophil migration by 30%, indicating enhanced immune response. Two cohort studies further supported these findings, showing GLP-1 use correlated with reduced prosthetic joint infections, fewer 90-day readmission rates, and reduced 2-year revisions in total knee and hip arthroplasty patients. Conclusion GLP-1s directly influence bone remodeling through receptor expression on osteocytes and bone mesenchymal stem cells. Emerging evidence suggests they may exert anabolic effects on bone, mitigate skeletal damage associated with obesity and diabetes, promote wound healing, and reduce perioperative complications. Despite these promising findings, long-term clinical data remains limited. Further research is essential to clarify their role and optimize their integration into perioperative management protocols for orthopedic patients.