Semaglutide pilot RCT protocol designed to optimize obese Asian adults for total knee arthroplasty

Obesity significantly increases perioperative complications, pain, and functional issues following total knee arthroplasty (TKA). Current preoperative weight management strategies show mixed results, highlighting a critical gap for effective optimization. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), like semaglutide, are potent weight-loss agents with potential metabolic and anti-inflammatory benefits beyond just weight reduction, making them appealing candidates for improving surgical outcomes. This protocol addresses the lack of randomized evidence for GLP-1RAs in perioperative TKA optimization, particularly in an Asian population.

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

This pilot trial is designed to determine the feasibility of conducting a definitive randomized trial in older Asian adults with obesity awaiting TKA. The study's primary objective is to estimate crucial operational metrics for a future larger trial. Specifically, it aims to quantify recruitment rates, participant adherence to the semaglutide regimen, the tolerability profile of the intervention, and overall participant retention over the 96-week study period. These feasibility outcomes are critical for informing the design and power calculations of a subsequent, fully powered RCT evaluating clinical efficacy. The protocol also outlines the collection of exploratory clinical outcomes, including changes in pain scores, body weight, and patient-reported functional outcomes, as well as the incidence of perioperative complications. These preliminary data will generate initial effect-size estimates, which are essential for determining the sample size required for a definitive trial. The study will also consider how semaglutide may influence perioperative outcomes through mechanisms beyond weight loss, such as its impact on metabolic and anti-inflammatory pathways, providing a broader understanding of its potential benefits.

The pilot trial is specifically designed to estimate recruitment, adherence, tolerability, and retention, and to generate preliminary effect-size estimates for a future fully powered trial.