Impact of Glucagon-Like Peptide-1 Receptor Agonists on Knee Arthroplasty Outcomes

Abstract Purpose Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for managing both obesity and diabetes mellitus, two major risk factors for adverse outcomes following total knee arthroplasty (TKA). Despite this, their potential role in pre-operative optimisation remains uncertain. The aim of this systematic review and meta-analysis was to assess whether the use of GLP-1 RAs is associated with improved post-operative outcomes in patients undergoing primary TKA. Methods A comprehensive literature search was conducted across MEDLINE, PubMed, Embase, and CENTRAL from inception to 1st June 2025. Eligible studies included adults (aged ≥ 18 years) undergoing primary TKA, comparing outcomes between GLP-1 RA users and non-users. Primary outcomes included surgical and medical complications. Secondary outcomes were hospital-related outcomes, including hospital readmissions and length of stay. Risk of bias and certainty of evidence were assessed using ROBINS-I and GRADE, respectively. Results Six retrospective cohort studies met the inclusion criteria which consisted of 20,074 GLP-1 RA users and 55,332 controls. Meta-analysis showed a statistically significant reduction in the odds of 90-day readmissions in comparison with control groups (OR 0.76, 95% CI 0.61–0.94; p = 0.01). No statistically significant associations were found for the remaining outcomes. Conclusions GLP-1 RA use was associated with reduced 90-day readmissions following TKA. However, significant heterogeneity limits the clinical applicability of these findings. Further prospective studies are warranted.