Protocol for Novel Perioperative Optimization of Obese Osteoarthritic Patients pending Total Knee Replacement with...

Obesity is associated with higher rates of perioperative complications and worse pain and functional outcomes after total knee arthroplasty (TKA). Preoperative optimization through weight management is therefore clinically appealing, but the current evidence base is mixed. No randomized controlled trial (RCT) has evaluated glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a perioperative optimization strategy before TKA, and no such trial has focused on an Asian population. This pilot randomized trial therefore aims to determine the feasibility, tolerability, and acceptability of semaglutide-based optimization before and after TKA in older Asian adults with obesity.

This is a two-arm pilot RCT that will recruit 54 adults aged 40 to 80 years with obesity (BMI ≥ 27 kg/m²) listed for primary TKA. Participants will be randomized 1:1 to semaglutide plus standard TKA care or to usual care alone. The intervention group will receive semaglutide for 48 weeks before and 48 weeks after TKA, with a planned four-week washout period before and after surgery. The control group will receive current standard care, including routine orthopaedic management and standardized general advice on diet and physical activity. Primary outcomes are feasibility outcomes (recruitment, adherence, tolerability, and retention), while pain, body weight, patient-reported outcomes, and perioperative complications are exploratory clinical outcomes intended to inform a future definitive trial.

This pilot trial will determine whether a definitive randomized trial is feasible in older Asian adults with obesity awaiting TKA. The study is designed to estimate recruitment, adherence, tolerability, and retention, and to generate preliminary effect-size estimates for a future fully powered trial. Because semaglutide may influence perioperative outcomes through mechanisms beyond weight loss alone, including metabolic and anti-inflammatory pathways, these pathways will be considered when interpreting the findings.