No Mid-Term Benefits of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Following Total Joint Arthroplasty

BACKGROUND: The aim of this systematic review was to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on medical complications, implant failure rates, and health-care-related costs in patients undergoing hip or knee arthroplasty. METHODS: A comprehensive search of electronic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trials Registry Platform (ICTRP), and the UK Clinical Trials Gateway, was conducted and was limited to studies from database inception to March 31, 2025. Inclusion criteria comprised randomized controlled trials or cohort studies involving adults (≥18 years old) undergoing total joint arthroplasty (TJA) while receiving a GLP-1 RA treatment of any dosage or duration. The risk of bias was assessed using the Cochrane risk-of-bias tool and ROBINS-I (Risk Of Bias In Non-Randomized Studies - of Interventions) assessment. Due to substantial heterogeneity in the study designs, a qualitative synthesis approach was employed. RESULTS: Eight retrospective studies met the inclusion criteria, encompassing 22,611 GLP-1 RA users and 77,810 controls. The mean patient age ranged from 56 to 64 years. Hospital readmission rates showed the most consistently favorable results among GLP-1 RA users, with 3 studies reporting significant reductions of 29% to 47% during the 90-day postoperative period. Five studies demonstrated that GLP-1 RA use was associated with significant reductions, ranging from 30% to 44%, in periprosthetic joint infection (PJI) rates, whereas 3 studies found no significant differences. Hospital resource utilization favored GLP-1 RA therapy, with several studies demonstrating shorter hospital stays and lower 90-day costs. Medical complications yielded variable results: some studies reported increased vascular and pulmonary events among GLP-1 RA users, whereas others observed reduced sepsis and hypoglycemic events in those patients. CONCLUSIONS: GLP-1 RA therapy was associated with reduced hospital readmissions and decreased hospital costs within 90 days postoperatively, although its benefits for PJI prevention showed mixed results, with some studies demonstrating significant reductions in PJI while others showed no difference. No consistent clinical advantages were observed at the 2-year follow-up. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.