Impact of GLP-1 Receptor Agonist Use on Total Knee Arthroplasty Outcomes in Metformin-Treated Diabetic Patients With and Without Comorbid Obesity: A Propensity-Matched Analysis

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been linked to improved outcomes following total knee arthroplasty (TKA). However, it remains unclear whether the observed benefits are attributable to weight loss, glycemic control, or first-line type 2 diabetes mellitus (T2DM) medications such as metformin. This study aimed to evaluate the impact of perioperative GLP-1RA use on TKA outcomes in T2DM patients stratified by obesity status. METHODS: The TriNetX Global Collaborative Network was queried using relevant Current Procedural Terminology and ICD-10 codes for metformin-treated T2DM patients aged 18 years or older undergoing primary TKA. Patients were divided into two groups based on obesity status and further stratified based on GLP-1RA use within three months of surgery. The groups were propensity matched (1:1) based on age, sex, body mass index (BMI), HbA1c, and comorbidities. Surgical outcomes, medical complications, and resource utilization were assessed at 90 days and 1 year. Surgical outcomes and revision rates were also assessed at two years. RESULTS: In obese patients (n = 8,170), GLP-1RA use was associated with notable reductions in postoperative anemia (odds ratio [OR] 0.714; P = 0.001), acute kidney injury (OR 0.755; P = 0.021), 90-day readmission (OR 0.776; P = 0.001), emergency department (ED) visits (OR 0.836; P = 0.008), and aseptic loosening at two years (OR 0.498; P = 0.037). These patients also demonstrated greater postoperative reductions in BMI and HbA1c. In nonobese patients (n = 1,328), GLP-1RA use was similarly associated with lower rates of 90-day readmission (OR 0.514; P = 0.004) and ED visits (OR 0.649; P = 0.024), although no notable differences in other outcomes were observed. CONCLUSION: Among metformin-treated T2DM patients undergoing TKA, GLP-1RA use was associated with reduced resource utilization irrespective of obesity. However, additional reductions in medical complications and aseptic loosening were observed in the obese group, suggesting a potential synergistic effect between weight loss and glycemic control. These findings highlight the effectiveness of GLP-1RAs in optimizing high-risk candidates undergoing TKA.