BACKGROUND: Obesity and diabetes mellitus (DM) pose challenges for patients undergoing total knee arthroplasty (TKA). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as agents for weight and DM management, but they affect multiple organ systems. Outcomes, trends, and demographics for perioperative GLP-1RA use in patients with TKA are not well understood. METHODS: A retrospective review of 13,751 primary, elective TKAs with at least 90 days of follow-up at an urban academic health system between 2012 and 2023 identified 865 patients who had perioperative GLP-1RA use. A 10:1 propensity score match based on sex, age, smoking status, American Society of Anesthesiologists classification, and body mass index created a control cohort of 8,650 TKAs with no GLP-1RA use. RESULTS: The use of GLP-1RAs varied significantly by race, Medicaid insurance, Charlson Comorbidity Index, and presence of DM. Black and Latino patients and those covered by Medicaid were significantly less likely to receive GLP-1RAs. The GLP-1RA group had significantly shorter length of stay (2.1 versus 2.5 days, P <
0.001) and a higher rate of home discharge (91.7 versus 84.2%, P <
0.001). The GLP-1RA users had significantly higher rates of 90-day emergency department visits (5.9 versus 4.0%, P = 0.008), but no differences in 90-day readmissions (4.3 versus 3.6%, P = 0.168) or 2-year revision (2.3 versus 2.6%, P = 0.362) compared to matched controls. The GLP-1RA patients had significantly lower all-cause revision rates at the last follow-up (2.7 versus 3.9%, P = 0.034), but there was no significant difference in Kaplan-Meier implant survival (P = 0.311). Before TKA, GLP-1RA patients had an average decrease in body mass index of 0.4, compared to an average increase of 1.2 for matched controls. CONCLUSIONS: Our results demonstrate that the use of GLP-1RAs is significantly lower for minority patients and those covered by Medicaid. Patients using GLP-1RAs have noninferior clinical outcomes with the potential for weight loss leading up to TKA. LEVEL OF EVIDENCE: III.