Glucagon-like peptide-1 receptor agonists in total joint arthroplasty: a comprehensive systematic review of what orthopaedic surgeons should know

Abstract

BACKGROUND: The rising prevalence of obesity and type 2 diabetes mellitus (T2DM) among patients undergoing total joint arthroplasty (TJA) presents a significant clinical challenge, increasing the risk of postoperative complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potential perioperative optimization strategy, but their impact on TJA outcomes remains debated. This systematic review was conducted to synthesize the evidence on the risks and benefits of GLP-1 RA use in adult patients undergoing primary TJA-specifically, total hip arthroplasty (THA), total knee arthroplasty (TKA), and total shoulder arthroplasty (TSA). METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Scopus, and Web of Science databases were searched from their inception to June 16, 2025, for studies comparing postoperative outcomes in adult patients undergoing primary total joint arthroplasty (TJA) and using GLP-1 RAs versus a control group. Data on study characteristics, patient demographics, and postoperative outcomes were extracted. Due to significant heterogeneity and overlap in data sources, a narrative synthesis rather than meta-analysis of the findings was conducted. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Fifteen retrospective cohort studies involving an aggregate total of 318,143 patients (114,365 THA, 125,505 TKA, 78,273 TSA) were included, with 56,132 receiving GLP-1 RAs. In THA and TKA, GLP-1 RAs use was associated with a reduced risk of periprosthetic joint infection (PJI) (e.g., 1.6% vs. 2.9% at 2 years for THA) and lower 90-day readmission rates (e.g., 1.1% vs. 2.0% for TKA and 1.6% vs. 2.0% for THA). When analyzed by exposure timing, the reduced PJI risk was most consistent in studies that defined GLP-1 RA use in the immediate perioperative period. Reported mean length of stay (LOS) was generally similar or slightly shorter among GLP-1 RA users compared to controls. Multiple studies reported either a reduction or no significant difference in the risk of 90-day emergency department visits. The short-term revision rates and dislocations were infrequent and did not differ significantly between groups in most of the included studies. In the TSA, evidence was inconsistent, with reduced odds of 90-day surgical site infection (SSI) (OR 0.25) in one study; however, no clear trend was observed. Gastrointestinal side effects and conflicting systemic risks were noted across procedures. CONCLUSION: Current observational data suggest that perioperative GLP-1 RA use in patients undergoing total hip or knee arthroplasty is not associated with a consistent increase in short-term revision rates and may be associated with a reduced risk of postoperative infection. Evidence regarding TSA remains inconclusive. However, given the retrospective nature of the evidence, substantial overlap in data sources, heterogeneity in exposure definitions, and short-term follow-up, these findings should be considered hypothesis-generating. Future prospective, randomized controlled trials with standardized exposure definitions and longer follow-up are required to confirm these associations and establish causality.